Vanda Pharmaceuticals Annual Report 2018

Plain-text annual report

Table of Contents UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549 Form 10-K ýANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended December 31, 2018¨TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF1934Commission File No. 001-34186 VANDA PHARMACEUTICALS INC.(Exact name of registrant as specified in its charter) Delaware03-0491827(State or other jurisdiction ofincorporation or organization)(I.R.S. EmployerIdentification No.)2200 Pennsylvania Avenue NW, Suite 300 EWashington D.C. 20037(202) 734-3400(Address and telephone number, including area code, of registrant’s principal executive offices)Securities registered pursuant to Section 12(b) of the Exchange Act:Title of Each ClassName of Each Exchange on Which RegisteredCommon Stock, par value $0.001The Nasdaq Stock Market LLC (Nasdaq Global Market)Rights to Purchase Series A Junior Participating Preferred StockThe Nasdaq Stock Market LLC(Nasdaq Global Market)Securities registered pursuant to Section 12(g) of the Exchange Act: None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ¨ No ýIndicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. Yes ¨ No ýIndicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filingrequirements for the past 90 days. Yes ý No ¨Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 ofRegulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit suchfiles). Yes ý No ¨Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to thebest of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to thisForm 10-K. ýIndicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or anemerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company”in Rule 12b-2 of the Exchange Act.Large accelerated filer ý Accelerated filer ¨Non-accelerated filer ¨ Smaller reporting company ¨ Emerging growth company ¨Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Securities Exchange Act of 1934). Yes ¨ No ýAs of June 30, 2018, the last business day of the registrant’s last completed second quarter, the aggregate market value of the Common Stock held bynon-affiliates of the registrant was approximately $974.3 million based on the closing price of the registrant’s Common Stock, as reported by The NasdaqGlobal Market, on such date. Shares of Common Stock held by each executive officer and director and stockholders known by the registrant to own 10% ormore of the outstanding stock based on public filings and other information known to the registrant have been excluded since such persons may be deemedaffiliates. This determination of affiliate status is not necessarily a conclusive determination for other purposes.The number of shares of the registrant’s Common Stock, par value $0.001 per share, outstanding as of February 12, 2019 was 52,642,754.The exhibit index as required by Item 601(a) of Regulation S-K is included in Item 15 of Part IV of this report.DOCUMENTS INCORPORATED BY REFERENCESpecified portions of the registrant’s proxy statement with respect to the registrant’s 2019 Annual Meeting of Stockholders, which is to be filed pursuantto Regulation 14A within 120 days after the end of the registrant’s fiscal year ended December 31, 2018, are incorporated by reference into Part III of thisForm 10-K. Table of ContentsVanda Pharmaceuticals Inc.Form 10-KTable of Contents PagePart I Cautionary Note Regarding Forward-Looking Statements1Item 1Business3Item 1ARisk Factors21Item 1BUnresolved Staff Comments48Item 2Properties49Item 3Legal Proceedings49Item 4Mine Safety Disclosures51Part IIItem 5Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities51Item 6Selected Consolidated Financial Data53Item 7Management’s Discussion and Analysis of Financial Condition and Results of Operations55Item 7AQualitative and Quantitative Disclosures about Market Risk66Item 8Financial Statements and Supplementary Data67Item 9Changes in and Disagreements with Accountants on Accounting and Financial Disclosure67Item 9AControls and Procedures67Item 9BOther Information68Part IIIItem 10Directors, Executive Officers and Corporate Governance68Item 11Executive Compensation68Item 12Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters68Item 13Certain Relationships and Related Transactions, and Director Independence68Item 14Principal Accountant Fees and Services68Part IVItem 15Exhibits and Financial Statement Schedules69Signatures70Exhibits102Table of ContentsPART ICAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements throughout this report are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995.Words such as, but not limited to, “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “project,” “target,” “goal,” “likely,” “will,” “would,” and“could,” or the negative of these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based uponcurrent expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differmaterially from those reflected in our forward-looking statements include, among others: •the ability of Vanda Pharmaceuticals Inc. (we, our, the Company or Vanda) to continue to commercialize HETLIOZ® (tasimelteon) for the treatmentof Non-24-Hour Sleep-Wake Disorder (Non-24) in the United States (U.S.) and Europe;•uncertainty as to the ability to increase market awareness of Non-24 and the market acceptance of HETLIOZ®;•our ability to continue to generate U.S. sales of Fanapt® (iloperidone) for the treatment of schizophrenia;•our dependence on third-party manufacturers to manufacture HETLIOZ® and Fanapt® in sufficient quantities and quality;•our level of success in commercializing HETLIOZ® and Fanapt® in new markets;•our ability to prepare, file, prosecute, defend and enforce any patent claims and other intellectual property rights;•our ability to reach agreement with the U.S. Food and Drug Administration (FDA) regarding our regulatory approval strategy, preclinical animaltesting requirements or proposed path to approval for tradipitant;•a loss of rights to develop and commercialize our products under our license agreements;•the ability to obtain and maintain regulatory approval of our products, and the labeling for any approved products;•the timing and success of preclinical studies and clinical trials;•a failure of our products to be demonstrably safe and effective;•the size and growth of the potential markets for our products and the ability to serve those markets;•our expectations regarding trends with respect to our revenues, costs, expenses, liabilities and cash, cash equivalents and marketable securities;•the scope, progress, expansion, and costs of developing and commercializing our products;•our failure to identify or obtain rights to new products;•a loss of any of our key scientists or management personnel;•limitations on our ability to utilize some or all of our prior net operating losses and orphan drug and research and development credits;•the cost and effects of litigation;•our ability to obtain the capital necessary to fund our research and development or commercial activities;•losses incurred from product liability claims made against us; and•use of our existing cash, cash equivalents and marketable securities. All written and verbal forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by thecautionary statements contained or referred to in this section. We caution investors not to rely too heavily on the forward-looking statements we make or thatare made on our behalf. We undertake no obligation, and specifically decline any obligation, to update or revise publicly any forward-looking statements,whether as a result of new information, future events or otherwise.1Table of ContentsWe encourage you to read Management’s Discussion and Analysis of our Financial Condition and Results of Operations and our consolidated financialstatements contained in this annual report on Form 10-K. We also encourage you to read Item 1A of Part I of this annual report on Form 10-K, entitled RiskFactors, which contains a more complete discussion of the risks and uncertainties associated with our business. In addition to the risks described above andin Item 1A of this report, other unknown or unpredictable factors also could affect our results. Therefore, the information in this report should be read togetherwith other reports and documents that we file with the Securities and Exchange Commission from time to time, including on Form 10-Q and Form 8-K, whichmay supplement, modify, supersede or update those risk factors. As a result of these factors, we cannot assure you that the forward-looking statements in thisreport will prove to be accurate. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of thesignificant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other personthat we will achieve our objectives and plans in any specified time frame, or at all.2Table of ContentsITEM 1.BUSINESSOverviewVanda Pharmaceuticals Inc. (we, our, the Company or Vanda) is a global biopharmaceutical company focused on the development andcommercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. We commenced operations in 2003 andour product portfolio includes: •HETLIOZ® (tasimelteon), a product for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24), was approved by the U.S. Food and DrugAdministration (FDA) in January 2014 and launched commercially in the U.S. in April 2014. In July 2015, the European Commission (EC) grantedcentralized marketing authorization with unified labeling for HETLIOZ® for the treatment of Non-24 in totally blind adults. HETLIOZ® wascommercially launched in Germany in August 2016. HETLIOZ® has potential utility in a number of other circadian rhythm disorders and ispresently in clinical development for the treatment of jet lag disorder, Smith-Magenis Syndrome (SMS) and Pediatric Non-24. An assessment of newHETLIOZ® clinical opportunities including the treatment of delayed sleep phase disorder and for sleep disorders in patients withneurodevelopmental disorders is ongoing.•Fanapt® (iloperidone), a product for the treatment of schizophrenia, the oral formulation of which was approved by the FDA in May 2009 andlaunched commercially in the U.S. by Novartis Pharma AG (Novartis) in January 2010. Novartis transferred all the U.S. and Canadian commercialrights to the Fanapt® franchise to us on December 31, 2014. Additionally, our distribution partners launched Fanapt® in Israel in 2014. Fanapt® haspotential utility in a number of other disorders. Initial clinical work studying a long acting injectable (LAI) formulation of Fanapt® began in 2018.An assessment of new Fanapt® clinical opportunities including the treatment of bipolar depression is ongoing.•Tradipitant (VLY-686), a small molecule neurokinin-1 receptor (NK-1R) antagonist, which is presently in clinical development for the treatment ofchronic pruritus in atopic dermatitis and the treatment of gastroparesis. An assessment of new tradipitant clinical opportunities including thetreatment of motion sickness is ongoing.•VTR-297, a small molecule histone deacetylase (HDAC) inhibitor presently in clinical development for the treatment of hematologic malignancies.•Portfolio of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activators and inhibitors. An early stage CFTR activator program isplanned for the treatment of dry eye and ocular inflammation. In addition, an early stage CFTR inhibitor program is planned for the treatment ofsecretory diarrhea disorders, including cholera.•VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist.Since we began operations in March 2003, we have devoted substantially all of our resources to the in-licensing, clinical development andcommercialization of our products. Our ability to generate meaningful product sales and achieve profitability largely depends on our level of success incommercializing HETLIOZ® and Fanapt® in the U.S. and Europe, on our ability, alone or with others, to complete the development of our products, includingtradipitant, and to obtain the regulatory approvals for and to manufacture, market and sell our products. The results of our operations will vary significantlyfrom year-to-year and quarter-to-quarter and depend on a number of factors, including risks related to our business, risks related to our industry, and otherrisks which are detailed in Item 1A of Part I entitled Risk Factors and Item 7 of Part II entitled Management’s Discussion and Analysis of Financial Conditionand Results of Operations of this annual report on Form 10-K.Our activities will necessitate significant uses of working capital in 2019 and beyond. We are currently concentrating our efforts on sellingHETLIOZ® and Fanapt® in the U.S. and our continued commercialization of HETLIOZ® in Europe. Additionally, we continue to pursue market approval ofHETLIOZ® and Fanapt® in other regions. We will continue to work with our distribution partner on the commercialization of Fanapt® outside the U.S. We seeopportunities to grow our commercial products through life cycle management strategies that include the addition of new indications and formulations. Wehave built a research and development organization that includes extensive expertise in the scientific disciplines of pharmacogenetics andpharmacogenomics. We operate cross-functionally and are led by an experienced research and development management team. Our pipeline includes novelprograms that could address largely unmet medical needs.Our founder and Chief Executive Officer, Mihael H. Polymeropoulos, M.D., started Vanda’s operations in early 2003 after establishing and leadingthe Pharmacogenetics Department at Novartis. In acquiring and developing our products, we have relied upon our deep expertise in the scientific disciplinesof pharmacogenetics and pharmacogenomics. These scientific disciplines examine both genetic variations among people that influence response to aparticular drug, and the multiple pathways through which drugs affect people.3Table of ContentsOur StrategyOur goal is to create a leading global biopharmaceutical company focused on developing and commercializing innovative therapies addressinghigh unmet medical needs through the application of our drug development expertise and our pharmacogenetics and pharmacogenomics expertise. The keyelements of our strategy to accomplish this goal are to: •Maximize the commercial success of HETLIOZ® and Fanapt®;•Enter into strategic partnerships to supplement our capabilities and to extend our commercial reach;•Pursue the clinical development and regulatory approval of our products;•Apply our pharmacogenetics and pharmacogenomics expertise to differentiate our products; and•Expand our product portfolio through the identification and acquisition of additional products.ProductsWe have the following products on the market:Product Indication Geography Select Historical MilestonesHETLIOZ®(tasimelteon) Non-24 United States FDA approval in January 2014;Commercial launch in April 2014 Europe EC approval in July 2015;Commercial launch in Germany in August 2016 Fanapt® (Oral)(iloperidone) Schizophrenia United States FDA approval in May 2009;Commercial launch in January 2010;U.S. and Canada rights sublicensed to Novartis in October 2009 and reacquired byVanda in December 2014;Long term maintenance supplemental New Drug Application (sNDA) approval in May2016 Fanaptum® (Oral)(iloperidone) Israel Market approval August 2012;Commercial launch in the fourth quarter of 2014 by our local distribution partner 4Table of ContentsWe have the following products in clinical development or under regulatory review:Product Target Indication Select Historical MilestonesHETLIOZ®(tasimelteon) Jet Lag Disorder Completed a Phase III clinical study (JET8) and reported results in the first quarter of2018;Completed a Phase II clinical study (JET) and reported results in the second quarter of2018;sNDA PDUFA-VI (as defined below) action target date of August 16, 2019 SMS Completed a placebo controlled study and reported results in the fourth quarter of 2018 Pediatric Non-24 Completed a pharmacokinetic study in the first quarter of 2018 Fanapt® (iloperidone) Schizophrenia Initiated a pharmacokinetic study of the LAI formulation in the fourth quarter of 2018 Other Disorders Potential indications are under evaluation including bipolar depression, majordepressive disorder and post-traumatic stress disorder – nightmares Tradipitant (VLY-686) Chronic Pruritus in AtopicDermatitis Completed a placebo controlled clinical study and reported results in the third quarter of2017;Initiated a Phase III study (EPIONE) in the second quarter of 2018 Gastroparesis Completed a placebo controlled study and reported results in the fourth quarter of 2018 VTR-297 Oncology Initiated a clinical study in patients with hematologic malignancies in the fourth quarterof 2018 VQW-765 CNS Disorders Potential indications are under strategic evaluation including cognitive impairment For more detailed information regarding our clinical trial results and regulatory activities for our products please refer to our press releases and SECfilings which can be found on the SEC Edgar system and on our website www.vandapharma.com.HETLIOZ® Commercial opportunity: Non-24In January 2014, HETLIOZ® was approved in the U.S. for the treatment of Non-24. Non-24 is a serious, rare and chronic circadian rhythm disordercharacterized by the inability to entrain (synchronize) the master body clock with the 24-hour day-night cycle. HETLIOZ® is the first FDA approvedtreatment for Non-24. HETLIOZ® is a melatonin agonist of the human MT1 and MT2 receptors, with greater specificity for MT2. These receptors are thoughtto be involved in the control of circadian rhythms. HETLIOZ® is believed to reset the master body clock in the suprachiasmatic nucleus, located in thehypothalamus, resulting in the entrainment and alignment of the body’s melatonin and cortisol rhythms to the 24-hour day-night cycle. HETLIOZ® waslaunched commercially in the U.S. in April 2014. In addition, in July 2015, the EC granted centralized marketing authorization with unified labeling forHETLIOZ® for the treatment of Non-24 in totally blind adults and included post-marketing commitments related to a pediatric investigation plan. Thisauthorization is valid in the 28 countries that are members of the European Union (E.U.), as well as European Economic Area members Iceland, Liechtensteinand Norway. HETLIOZ® was launched commercially in Germany in August 2016.In January 2010, the FDA granted orphan drug designation status for HETLIOZ® in Non-24 in blind individuals. The FDA grants orphan drugdesignation to drugs that may provide significant therapeutic advantage over existing treatments and target conditions affecting 200,000 or fewer U.S.patients per year. Orphan drug designation provides potential financial and regulatory incentives, including study design assistance, tax credits, waiver ofFDA user fees, and up to seven years of market exclusivity upon marketing approval. In February 2011, the European Medicines Agency (EMA) designatedHETLIOZ® as an orphan medicinal product for the same indication.Non-24 affects a majority of totally blind individuals, or approximately 80,000 people in the U.S. Blind individuals who develop Non-24 lack thelight sensitivity necessary to synchronize the master body clock in the brain with the 24-hour day-night cycle. Non-24 also affects certain sightedindividuals. In these sighted individuals, decreased exposure or sensitivity5Table of Contentsto light and social and physical activity cues may contribute to a free-running circadian rhythm. With the high frequency of mental disorders involvingsocial isolation and cases of Non-24 developing after a change in sleep habits, behavioral factors in combination with physiological tendency mayprecipitate and perpetuate this disorder in sighted individuals. Hospitalized individuals with neurological and psychiatric disorders can become insensitiveto social cues, predisposing them to the development of Non-24.Most people have a master body clock that naturally runs longer than 24-hours and light is the primary environmental cue that resets it to 24 hourseach day. Individuals with Non-24 have a master body clock that is not reset, and continually delays, resulting in prolonged periods of misalignmentbetween their circadian rhythms and the 24-hour day-night cycle, including the timing of melatonin and cortisol secretion. As a result of this misalignment,Non-24 is associated with significant disruption of the sleep-wake cycle and impairments in social and occupational functioning, and marked subjectivedistress. Individuals with Non-24 cycle in-and out-of phase and suffer from disrupted nighttime sleep patterns and/or excessive daytime sleepiness.While there are no FDA or EC approved treatments for Non-24 other than HETLIOZ®, there are a number of drugs approved and prescribed forpatients with sleep disorders. The most commonly prescribed drugs are hypnotics. See Competition below for a discussion of commonly prescribed drugs forpatients with sleep disorders.Therapeutic opportunity: Circadian Rhythm Sleep DisordersSleep disorders are segmented into three major categories: primary insomnia, secondary insomnia and circadian rhythm sleep disorders (CRSDs).Insomnia is a symptom complex that comprises difficulty falling asleep or staying asleep, or non-refreshing sleep, in combination with daytime dysfunctionor distress. The symptom complex can be an independent disorder (primary insomnia) or be a result of another condition such as depression or anxiety(secondary insomnia). CRSDs result from a misalignment of the sleep/wake cycle and an individual’s daily activities or lifestyle. The circadian rhythm is therhythmic output of the human biological clock and is governed by the hormones melatonin and cortisol. Both the timing of behavioral events (activity,sleep, and social interactions) and the environmental light/dark cycle result in a sleep/wake cycle that follows the circadian rhythm. Examples of CRSDsinclude transient disorders such as jet lag and chronic disorders such as delayed sleep phase disorder, shift work sleep disorder and Non-24.In March and May 2018, respectively, we announced the results of our JET and JET8 studies for the treatment of jet lag disorder. In the JET8 study,318 healthy volunteers were admitted to a sleep unit and were subjected to a circadian challenge of an 8 hours advance to their usual bedtime. The JET8study design induced the circadian challenge experienced by travelers who cross 8 times zones, which leads to jet lag disorder. This clinical design allowedfor the study of HETLIOZ® without the confounding effects of sleep deprivation and variable light conditions. In the JET8 clinical study, HETLIOZ®demonstrated significant and clinically meaningful benefits in nighttime and daytime symptoms of jet lag disorder. The JET study was a two-phasetransatlantic travel study, with an observational travel phase (baseline) followed by a treatment phase. Study participants traveled either 5 or 8 time zonesfrom Washington, DC to London and San Francisco or Los Angeles to London, respectively. The JET study showed effectiveness in treating travelers whoflew from the U.S. to the United Kingdom. The FDA accepted the filing of our sNDA for HETLIOZ® for the treatment of jet lag disorder in December 2018.The FDA determined the action target date under the Prescription Drug User Fee Act Amendments of 2017 (PDUFA-VI) to be August 16, 2019. Jet lagdisorder affects millions of individuals annually who cross multiple time zones during their travel. Jet lag disorder symptoms are more severe during eastwardtravel. U.S. Department of Commerce, International Trade Administration reports state that more than 20 million U.S. residents make trips abroad each year tooverseas destinations in Europe, the Middle East and Asia.We reported results from a SMS placebo controlled study in December 2018, which showed that HETLIOZ® improved sleep quality and increasedsleep duration in patients with SMS. SMS is a rare genetic disorder caused by a deletion on chromosome 17. The U.S. National Institute of Health estimatesthat SMS affects approximately one in 15,000 to 25,000 births in the U.S.We are planning to develop HETLIOZ® for the treatment of pediatric Non-24. A pharmacokinetic study of the HETLIOZ® pediatric liquidformulation was completed in the first quarter of 2018. Additionally, in September 2018 we announced results from a driving study which demonstrated thattasimelteon did not impair measures of driving performance. An assessment of new HETLIOZ® clinical opportunities including the treatment of delayed sleepphase disorder and for sleep disorders in patients with neurodevelopmental disorders is ongoing.6Table of ContentsFanapt® Commercial Opportunity: SchizophreniaFanapt® is a product for the treatment of schizophrenia. In May 2009, the FDA granted U.S. marketing approval of Fanapt® for the acute treatment ofschizophrenia in adults. In October 2009, we entered into an amended and restated sublicense agreement with Novartis. We had originally entered into asublicense agreement with Novartis in June 2004 pursuant to which we obtained certain worldwide exclusive licenses from Novartis relating to Fanapt®.Pursuant to the amended and restated sublicense agreement, Novartis had exclusive commercialization rights to all formulations of Fanapt® in the U.S. andCanada. In January 2010, Novartis launched Fanapt® in the U.S. On December 31, 2014, Novartis transferred all the U.S. and Canadian commercial rights tothe Fanapt® franchise to us as part of a settlement agreement. In May 2016, the FDA approved a sNDA for Fanapt® for the maintenance treatment ofschizophrenia in adults.In July 2017, the EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion recommending against approval ofFanaptum® (oral iloperidone tablets) for the treatment of schizophrenia in adult patients in the E.U. The CHMP was of the opinion that the benefits ofFanaptum® did not outweigh its risks and recommended against marketing authorization. The negative opinion was upheld upon appeal in November 2017.Schizophrenia is a chronic, debilitating mental disorder characterized by hallucinations, delusions, racing thoughts and other psychotic symptoms(collectively referred to as “positive symptoms”), as well as moodiness, anhedonia (inability to feel pleasure), loss of interest, eating disturbances andwithdrawal (collectively referred to as “negative symptoms”), and attention and memory deficits (collectively referred to as “cognitive symptoms”).Schizophrenia develops in late adolescence or early adulthood in approximately 1% of the world’s population. Most schizophrenia patients today are treatedwith drugs known as “atypical” antipsychotics, which were first approved in the U.S. in the late 1980s. These antipsychotics have been named “atypical” fortheir ability to treat a broader range of negative symptoms than the first-generation “typical” antipsychotics, which were introduced in the 1950s and are nowgeneric. Atypical antipsychotics are generally regarded as having improved side effect profiles and efficacy relative to typical antipsychotics. SeeCompetition below for a discussion of commonly prescribed atypical antipsychotics in addition to Fanapt®.Therapeutic opportunity: OtherIn October 2018, we enrolled our first patient in a pharmacokinetic study of the LAI formulation of Fanapt®. An assessment of new Fanapt® clinicalopportunities including the treatment of bipolar depression, major depressive disorder and post-traumatic stress disorder-nightmares is ongoing.Tradipitant (VLY-686)Tradipitant is a small molecule NK-1R antagonist that we licensed from Eli Lilly and Company (Lilly) in April 2012. NK-1R antagonists have beenevaluated in a number of indications including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, alcohol dependence,anxiety, depression, gastroparesis and chronic pruritus in atopic dermatitis, psoriasis and prurigo nodularis.We announced results in September 2017 from a randomized Phase II clinical study of tradipitant as a monotherapy in the treatment of chronicpruritus in patients with atopic dermatitis. Tradipitant was shown to improve the intensity of the worst itch patients experienced, as well as atopic dermatitisdisease severity. On the pre-specified primary endpoint of Average Itch Visual Analog Scale (VAS), tradipitant showed improvement over placebo, but thisimprovement was not significant due to high placebo effect and the lack of sensitivity of this measure. In June 2018, we initiated EPIONE, a Phase III study oftradipitant for chronic pruritus in atopic dermatitis.Atopic dermatitis is a chronic, relapsing inflammatory skin disorder characterized by the symptom of intense and persistent pruritus or itch. Otherclinical features include erythema, excoriation, edema, lichenification, oozing and xerosis. Atopic dermatitis is a common skin disorder affecting millions ofpeople worldwide. Currently there are very few safe systemic treatments available for atopic dermatitis, representing a significant unmet medical need in thispopulation. A 2015 Decision Resources Group report estimated that 9.8 million individuals were diagnosed with atopic dermatitis in the U.S. of whichapproximately 6.4 million were drug-treated atopic dermatitis patients.We announced results in December 2018 from a randomized clinical study (2301) of tradipitant as a monotherapy in the treatment of gastroparesis.Several symptom severity scales were used to assess gastroparesis symptoms, including the Gastroparesis Symptom Index (GCSI), Patients Assessment ofUpper Gastrointestinal Disorders-Symptoms (PAGI-SYM), and7Table of ContentsPatient Global Impression of Change (PGI-C) as well as a Clinician Global Impression of Severity (CGI-S). Tradipitant met the primary endpoint of the studyof change in nausea score as measured by patient daily diaries and also met the related endpoint of improvement in the number of nausea free days.Tradipitant also showed significant improvement in most of the secondary endpoints studied, including the several key scales reflecting overall gastroparesissymptoms, specifically GCSI, PAGI-SYM, CGI-S, and PGI-C.Gastroparesis is a serious medical condition characterized by delayed gastric emptying associated with the symptoms of nausea, vomiting, bloating,fullness after meals and abdominal pain, along with significant impairment of social and occupational functioning. A paper by Rey et al published in theJanuary 2012 Journal of Neurogastroenterology and Motility estimated the prevalence of gastroparesis in the U.S. to be over 5 million patients, many ofwhom remain undiagnosed.An assessment of new tradipitant clinical opportunities including the treatment of motion sickness is ongoing.In April 2018, we submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) period for patients who hadcompleted the tradipitant Phase II clinical study (2301) in gastroparesis. In May 2018, based on feedback from the FDA, we amended the protocol limitingthe duration of treatment in the 2301 study to a total of three months, while continuing to seek further dialogue with the FDA on extending the studyduration to 52-weeks. As a part of this negotiation process, in September 2018, we submitted a new follow-on 52-week OLE protocol to the FDA (2302) forpatients who had completed the 2301 study. While waiting for further feedback, no patients were ever enrolled in any study beyond 12 weeks. On December19, 2018, the FDA imposed a partial clinical hold (PCH) on the two proposed studies, stating that we are required first to conduct additional chronic toxicitystudies in canines, monkeys or minipigs before allowing patients access in any clinical protocol beyond 12 weeks. The PCH was not based on any safety orefficacy data related to tradipitant. Rather, the FDA informed us that these additional toxicity studies are required by a guidance document. We do not expectthe PCH to have any material impact on our ongoing clinical studies in atopic dermatitis and motion sickness or the planned Phase III study in gastroparesis.At present, the PCH has not had any impact on the potential timing of an NDA filing or approval for these indications. We will continually reassess thissituation as events unfold.On February 5, 2019, we filed a lawsuit against the FDA in the United States District Court for the District of Columbia, challenging the FDA’s legalauthority to issue the PCH, and seeking an order to set it aside. On February 14, 2019, the FDA filed a Motion for Voluntary Remand to the Agency and for aStay of the Case. We intend to continue vigorously pursuing our interests in the matter (see Part I, Item 3, Legal Proceedings of this annual report on Form10-K for additional information).VTR-297VTR-297 is a small molecule HDAC inhibitor with potential use as a treatment for several oncology indications. The FDA accepted anInvestigational New Drug (IND) application for VTR-297 in 2017 and provided authorization to proceed with the treatment of patients with relapsed and/orrefractory hematologic malignancies. We initiated a clinical study in patients with hematologic malignancies in the fourth quarter of 2018.VQW-765VQW-765 is a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist that we licensed from Novartis on December 31, 2014 pursuant to asettlement agreement. We are evaluating potential indications, including cognitive impairment.License AgreementsOur rights to develop and commercialize our products are subject to the terms and conditions of licenses granted to us by other pharmaceuticalcompanies.HETLIOZ® In February 2004, we entered into a license agreement with Bristol-Myers Squibb (BMS) under which we received an exclusive worldwide licenseunder certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize HETLIOZ®. As a result of the FDA’sapproval of the HETLIOZ® New Drug Application (NDA) in January 2014, we made an $8.0 million milestone payment to BMS in the first quarter of 2014under the license agreement that was capitalized as an intangible asset and is being amortized over the estimated economic useful life of the related productpatents for HETLIOZ® in the U.S. In April 2018, we met another milestone under our license agreement when cumulative worldwide8Table of Contentssales of HETLIOZ® reached $250.0 million. As a result of the achievement of this milestone, we made a payment to BMS of $25.0 million in June 2018. Wehave no remaining milestone obligations to BMS. Additionally, we are obligated to make royalty payments on HETLIOZ® net sales to BMS in any territorywhere we commercialize HETLIOZ® for a period equal to the greater of 10 years following the first commercial sale in the territory or the expiry of the newchemical entity (NCE) patent in that territory. During the period prior to the expiry of the NCE patent in a territory, we are obligated to pay a 10% royalty onnet sales in that territory. The royalty rate is decreased by half for countries in which no NCE patent existed or for the remainder of the 10 years after theexpiry of the NCE patent. We are also obligated under the license agreement to pay BMS a percentage of any sublicense fees, upfront payments andmilestone and other payments (excluding royalties) that we receive from a third-party in connection with any sublicensing arrangement, at a rate which is inthe mid-twenties. We have agreed with BMS in the license agreement for HETLIOZ® to use commercially reasonable efforts to develop and commercializeHETLIOZ®. Either party may terminate the HETLIOZ® license agreement under certain circumstances, including a material breach of the agreement by theother. In the event we terminate our license, or if BMS terminates our license due to our breach, all rights licensed and developed by us under this agreementwill revert or otherwise be licensed back to BMS on an exclusive basis.Fanapt® Pursuant to the terms of a settlement agreement with Novartis, Novartis transferred all U.S. and Canadian rights in the Fanapt® franchise to us onDecember 31, 2014. We were obligated to make royalty payments to Sanofi S.A. (Sanofi) and Titan Pharmaceuticals Inc. (Titan) at a percentage rate equal to23% on annual U.S. net sales of Fanapt® up to $200.0 million, and at a percentage rate in the mid-twenties on sales over $200.0 million through November2016. In February 2016, we amended the agreement with Sanofi and Titan to remove Titan as the entity through which royalty payments from Vanda aredirected to Sanofi following the expiration of the NCE patent for Fanapt® in the U.S. on November 15, 2016. Under the amended agreement, we pay directlyto Sanofi a fixed royalty of 3% of net sales from November 16, 2016 through December 31, 2019 related to manufacturing know-how. We made a$2.0 million pre-payment during the year ended December 31, 2016 that applied to this 3% manufacturing know-how royalty. No further royalties onmanufacturing know-how are payable by us after December 31, 2019. This amended agreement did not alter Titan’s obligation under the license agreement tomake royalty payments to Sanofi prior to November 16, 2016 or our obligation to pay Sanofi a fixed royalty on Fanapt® net sales equal up to 6% onSanofi know-how not related to manufacturing under certain conditions for a period of up to 10 years in markets where the NCE patent has expired or was notissued. We may lose our rights to develop and commercialize Fanapt® if we fail to comply with certain requirements in the Titan license agreement regardingour financial condition, or if we fail to comply with certain diligence obligations regarding our development or commercialization activities.Tradipitant (VLY-686)In April 2012, we entered into a license agreement with Lilly pursuant to which we acquired an exclusive worldwide license under certain patentsand patent applications, and other licenses to intellectual property, to develop and commercialize an NK-1R antagonist, tradipitant, for all humanindications. The patent describing tradipitant as a NCE expires in April 2023, except in the U.S., where it expires in June 2024 absent any applicable patentterm adjustments. Lilly is eligible to receive future payments based upon achievement of specified development and commercialization milestones as well astiered-royalties on net sales at percentage rates up to the low double digits. These milestones include $4.0 million for pre-NDA approval milestones, $10.0million and $5.0 million for the first approval of a marketing authorization for tradipitant in the U.S. and E.U., respectively, and up to $80.0 million for salesmilestones. The $4.0 million of pre-NDA approval milestones includes $2.0 million due upon enrollment of the first subject into a Phase III study fortradipitant and $2.0 million due upon the filing of the first marketing authorization for tradipitant in either the U.S. or the E.U. As a result of enrolling the firstsubject into a Phase III study for tradipitant in July 2018, we made a $2.0 million milestone payment to Lilly. We are obligated to use commerciallyreasonable efforts to develop and commercialize tradipitant. Either party may terminate the agreement under certain circumstances, including a materialbreach of the agreement by the other. In the event that we terminate the agreement, or if Lilly terminates the agreement due to our breach or for certain otherreasons set forth in the agreement, all rights licensed and developed by us under the agreement will revert or otherwise be licensed back to Lilly on anexclusive basis, subject to payment by Lilly to us of a royalty on net sales of products that contain tradipitant.VQW-765In connection with the settlement agreement with Novartis relating to Fanapt®, we received an exclusive worldwide license under certain patents andpatent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptorpartial agonist. Pursuant to the license agreement, we are obligated to use commercially reasonable efforts to develop and commercialize VQW-765 and areresponsible for all9Table of Contentsdevelopment costs. We have no milestone obligations, but Novartis is eligible to receive tiered-royalties on net sales at percentage rates up to the mid-teens.Either party may terminate the agreement under certain circumstances, including a material breach of the agreement by the other. In the event thatwe terminate the agreement, or if Novartis terminates the agreement due to our breach or for certain other reasons set forth in the agreement, all rights licensedand developed by us under the agreement will revert or otherwise be licensed back to Novartis on an exclusive basis, subject to payment by Novartis to us ofa royalty on net sales of products that contain VQW-765.Portfolio of CFTR activators and inhibitorsIn March 2017, we entered into a license agreement with the University of California San Francisco (UCSF), under which we acquired an exclusiveworldwide license to develop and commercialize a portfolio of CFTR activators and inhibitors. Pursuant to the license agreement, we will develop andcommercialize the CFTR activators and inhibitors and are responsible for all development costs under the license agreement, including current pre-investigational new drug development work. UCSF is eligible to receive future payments based upon achievement of specified development andcommercialization milestones as well as single-digit tiered-royalties on net sales. These milestones include an initial license fee of $1.0 million, which waspaid by us in the first quarter of 2017, annual maintenance fees, $12.4 million for pre-NDA approval milestones and $33.0 million for future regulatoryapproval and sales milestones. Included in the $12.4 million in pre-NDA approval milestones is a $350,000 milestone due upon the conclusion of a Phase Istudy for each licensed product but not to exceed $1.1 million in total for the CFTR portfolio. In the fourth quarter of 2018, we determined the first pre-NDAapproval milestone to be probable and accrued a current liability of $0.2 million as of December 31, 2018.Either party may terminate the agreement under certain circumstances. In the event that we terminate the agreement, or if UCSF terminates theagreement due to our breach or for certain other reasons set forth in the agreement, all rights licensed and developed by us under the agreement will revert orotherwise be licensed back to UCSF. Termination will not relieve us of our obligation to pay royalties or other payments owed, if any, to UCSF under theterms of the agreement.Patents and proprietary rights; Hatch-Waxman protectionWe will be able to protect our products from unauthorized use by others only to the extent that our products are covered through regulatoryprotections or by valid and enforceable patents, either licensed to us by others or generated through our activities internally, that give us sufficientproprietary rights. Accordingly, securing patents, regulatory data package protection, and other proprietary rights is an essential element of our businessstrategies.HETLIOZ®, tradipitant and VQW-765 are covered by NCE and other patents and patent applications related to their respective medicinal uses. Inaddition, NCE patent protection has been sought for VTR-297 and CFTR. Patent applications for these active ingredients remain pending. While the NCEpatents protecting Fanapt® have expired, Fanapt® remains protected by medicinal patents. For more on the license and sublicense arrangements related tothese active ingredients, see License Agreements above. In addition, we have filed for patents based on our own discoveries that seek to provide additionalprotection for HETLIOZ® and Fanapt®.10Table of ContentsThe table below is a summary of Orange Book listed patents for our commercial products. Members of these patent families are also issued orpending in a number of major market territories, such as Europe and Japan. Number TypeHETLIOZ® US 5,856,529 New chemical entity US 9,060,995 Method of treatment US 9,539,234 Method of treatment US 9,549,913 Method of treatment US 9,730,910 Method of treatment US 9,855,241 Method of treatment US RE46604 Method of treatment US 10,071,977 Drug substance US 10,149,829 Method of treatmentFanapt® US 8,586,610 Method of treatment US 8,652,776 Method of treatment US 8,999,638 Method of treatment US 9,072,742 Method of treatment US 9,074,254 Method of treatment US 9,074,255 Method of treatment US 9,074,256 Method of treatment US 9,138,432 Method of treatment US 9,157,121 Method of treatmentHETLIOZ® Our rights to the NCE patent covering HETLIOZ® and related intellectual property have been acquired through a license with BMS. HETLIOZ® andits formulations, genetic markers and uses are the subject of numerous patent filings for which protection has been sought in selected countries worldwide.The NCE patent covering HETLIOZ® expires in December 2022 in the U.S., which is inclusive of a five-year extension granted under the Hatch-Waxman Actin October 2018. Corresponding NCE patent protection has expired in most other markets. The U.S. Patent and Trademark Office has issued seven method ofuse patents for HETLIOZ® that will expire during 2033 and 2034 and one drug substance patent that will expire in 2035.In Europe, the law provides for ten years of data exclusivity (with the potential for an additional year if the drug is developed for a significant newindication). As such, in Europe, data exclusivity will protect HETLIOZ® for at least ten years from approval. A completed Pediatric Investigation Plan couldfurther extend this exclusivity for two years in an orphan indication, for a total of 12 years of exclusivity. It is also possible that the term of the new chemicalentity patent in Europe could be extended by issuance of a supplementary protection certificate (SPC). The European Patent Office has granted our patentapplication directed to the 20 mg/day dose. This patent will expire normally in 2027. Other pending patent applications in Europe, if granted, may offeradditional protection for HETLIOZ®.Outside the U.S. and Europe, data exclusivity will protect HETLIOZ® from generic competition for varying numbers of years depending on thecountry.Additional patent applications directed to specific sleep disorders and to methods of treating patients with HETLIOZ®, if issued, would provideexclusivity for such indications and methods of treatment, potentially extending the effective patent protection period in the U.S., Europe, and other majormarkets.Fanapt® The NCE patent for Fanapt®, which expired in 2016 in the U.S. and in 2010 in other major market countries, was owned by Sanofi. Other patents andpatent applications relating to Fanapt® previously owned by Novartis are now owned by Vanda. We originally obtained exclusive worldwide rights todevelop and commercialize the products covered by these patents11Table of Contentsthrough license and sublicense arrangements. Then, pursuant to an amended sublicense agreement with Novartis, Novartis retained exclusivecommercialization rights to all formulations of Fanapt® in the U.S. and Canada. However, as of December 2014, pursuant to an asset transfer agreement, weacquired all rights in Fanapt®, including in the U.S. and Canada.Fanapt® metabolites, formulations, genetic markers and uses are the subject of numerous patent filings in which protection has been sought in theU.S., Europe, and other markets. In November 2013, a U.S. patent directed to a method of treating patients with Fanapt® based on genotype was issued to usby the U.S. Patent and Trademark Office. This patent, which was listed in the Orange Book in January 2015, is set to expire in 2027, potentially furtherextending the U.S. marketing exclusivity for Fanapt®. Additional method of treatment patents have been issued in the U.S. and listed in the Orange Book,with the latest expiration date in December 2031. See Note 16, Legal Matters, to the consolidated financial statements included in Part II of this annual reporton Form 10-K for additional information.In Europe, the law provides for ten years of regulatory exclusivity (with the potential for an additional year if the drug is developed for a significantnew indication). No generic versions of Fanapt® would be permitted to be marketed or sold during the applicable regulatory exclusivity period in mostEuropean countries. Outside the U.S. and Europe, similar regulatory package protection periods may be available and could protect Fanapt® from genericcompetition for varying numbers of years depending upon the country. Several other patent applications covering metabolites, uses, formulations andgenetic markers relating to Fanapt® could provide protection extending beyond 2020. Patents sought for the microsphere LAI formulation of Fanapt® expirein 2024 in the U.S. and 2022 in most of the major markets in Europe. Patents sought for the aqueous microcrystals LAI formulation of Fanapt® expire in 2023in the U.S. and in most of the major markets in Europe.TradipitantLilly owns an NCE patent as well as patent applications directed to polymorphic forms of, and methods of making tradipitant. This patent protectionwas sought in the U.S. and in other countries worldwide. These patents and patent applications have been licensed to us. The NCE patent covering tradipitantexpires in 2023, except in the U.S., where it expires normally in 2024, subject to any extension that may be received under Hatch-Waxman. We have filedadditional patent applications based on discoveries made during recent studies with tradipitant.VQW-765Novartis owns a NCE patent as well as patent applications directed to methods of using VQW-765, VQW-765 formulations, and combinations ofVQW-765 with other active pharmaceutical ingredients. In connection with the settlement agreement with Novartis relating to Fanapt®, we received anexclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist. The NCE patent expires normally in 2023 in the U.S., Europe, and other markets.VTR-297VTR-297 is a small molecule HDAC inhibitor with potential use as a treatment for several oncology indications. We have pending patentapplications covering the use of VTR-297 and plan on filing additional applications based on discoveries made throughout the development plan of thismolecule.Portfolio of CFTR activators and inhibitorsOur portfolio of CFTR activators and inhibitors may have broad applicability in addressing a number of high unmet medical needs, includingchronic dry eye, constipation, polycystic kidney disease, cholestasis and secretory diarrheas. We plan on filing applications based on discoveries madethroughout the development plan of these compounds.Other PatentsAside from the NCE patents and other in-licensed patents relating to Fanapt®, HETLIOZ®, tradipitant and VQW-765, we have obtained or filednumerous patent and patent applications, most of which have been filed in key markets including the U.S., relating to our products and developmentcompounds. In addition, we have filed numerous other patent applications relating to drugs not presently in clinical studies. The claims in these variouspatents and patent applications are directed to compositions of matter, including claims covering other products, pharmaceutical compositions and methodsof use.12Table of ContentsProprietary Know-howFor proprietary know-how that is not appropriate for patent protection, processes for which patents are difficult to enforce and any other elements ofour discovery process that involve proprietary know-how and technology that are not covered by patent applications, we generally rely on trade secretprotection and confidentiality agreements to protect our interests. We require all of our employees, relevant consultants and advisors to enter intoconfidentiality agreements. Where it is necessary to share our proprietary information or data with outside parties, our policy is to make available only thatinformation and data required to accomplish the desired purpose and only pursuant to a duty of confidentiality on the part of those parties.Marketing and SalesHETLIOZ® was approved in the U.S. for the treatment of Non-24 in January 2014 and commercially launched in the U.S. in April 2014.Additionally, HETLIOZ® was approved in the E.U. for the treatment of Non-24 in totally blind adults in July 2015. We commercially launched HETLIOZ® inGermany in August 2016.Given the range of potential indications for HETLIOZ®, we may pursue one or more partnerships for the development and commercialization ofHETLIOZ® worldwide.Fanapt® was approved in the U.S. for the treatment of schizophrenia in May 2009 and commercially launched in the U.S. in January 2010. In October2009, we entered into an amended and restated sublicense agreement with Novartis pursuant to which Novartis has exclusive commercialization rights to allformulations of Fanapt® in the U.S. and Canada. Novartis began selling Fanapt® in the U.S. during the first quarter of 2010. Pursuant to the terms of asettlement agreement with Novartis, Novartis transferred all U.S. and Canadian rights in the Fanapt® franchise to us on December 31, 2014. We continue toexplore the regulatory path and commercial opportunity for Fanapt® oral formulation in other regions.ManufacturingWe currently utilize a virtual supply manufacturing and distribution chain in which we do not have our own facilities to manufacture commercial orclinical trial supplies of drugs and we do not have our own distribution facilities. Additionally, we do not intend to develop such facilities for any product inthe near future. Instead, we contract with third parties for the manufacture, warehousing, order management, billing and collection and distribution of ourproducts and product candidates.We expect to continue to rely solely on third-party manufacturers to manufacture drug substance and final drug products for both clinicaldevelopment and commercial sale. However, there are numerous factors that could cause interruptions in the supply of our products, including regulatoryreviews, changes in our sources for manufacturing, disputes with a manufacturer, or financial instability of manufacturers, all of which could negativelyimpact our operation and our financial results.We have agreements in place with Patheon Pharmaceuticals Inc. and Patheon Inc. (collectively, Patheon), subsidiaries of Thermo Fisher Scientific,for the manufacture of HETLIOZ® and Fanapt®.In January 2014, we entered into a manufacturing agreement with Patheon for the manufacture of commercial supplies of HETLIOZ® 20 mg capsulesat Patheon’s Cincinnati, Ohio manufacturing site. Under the HETLIOZ® manufacturing agreement, we are responsible for supplying the active pharmaceuticalingredient (tasimelteon) for HETLIOZ® to Patheon and have agreed to certain minimum yearly order requirements. Patheon is responsible for manufacturingthe HETLIOZ® 20 mg capsules, conducting quality control and stability testing, and packaging the HETLIOZ® capsules. The HETLIOZ® manufacturingagreement has an initial term of five years and will automatically renew after the initial term for successive terms of one year each, unless either party givesnotice of its intention to terminate the agreement at least twelve months prior to the end of the then current term. Either party may terminate the HETLIOZ®manufacturing agreement under certain circumstances upon specified written notice to the other party.As part of a settlement agreement, we assumed Novartis’ manufacturing agreement with Patheon for the manufacture of commercial supplies ofFanapt®. In May 2016, we entered into a new manufacturing agreement with Patheon for the manufacture of commercial supplies of Fanapt® 1, 2, 4, 6, 8, 10and 12 mg tablets at Patheon’s Mississauga, Ontario, Canada manufacturing site. Under the Fanapt® manufacturing agreement, we are responsible forsourcing the supply of the active pharmaceutical ingredient (iloperidone), and have agreed to order from Patheon at least 70% of the total yearly requirementof new units of Fanapt® tables for the U.S. and other specified countries each year for the term of the agreement. The Fanapt® manufacturing agreement has aninitial term of five years and will automatically renew after the initial term for successive13Table of Contentsterms of one year each, unless either party gives notice of its intention to terminate the agreement at least twelve months prior to the end of the then currentterm. Either party may terminate the Fanapt® manufacturing agreement under certain circumstances upon specified written notice to the other party.Research and DevelopmentWe have built a research and development organization that includes extensive expertise in the scientific disciplines of pharmacogenetics andpharmacogenomics. We operate cross-functionally and are led by an experienced research and development management team. We use rigorous projectmanagement techniques to assist us in making disciplined strategic research and development program decisions and to help limit the risk profile of ourproduct pipeline. We also access relevant market information and key opinion leaders in creating target product profiles and, when appropriate, as weadvance our programs towards commercialization. We engage third parties to conduct portions of our preclinical research. In addition, we utilize multipleclinical sites to conduct our clinical trials; however, we are not substantially dependent upon any one of these sites for our clinical trials nor do any of themconduct a major portion of our clinical trials.Major CustomersOur revenues are generated from product sales and are concentrated with specialty pharmacies, including Diplomat Pharmacy, Inc. and Accredo (asubsidiary of Express Scripts), and wholesalers, including Cardinal Health, Inc., AmerisourceBergen Drug Corporation, and McKesson Corporation. These 5major customers each accounted for more than 10% of total revenues and, as a group, represented 92% of total revenues for the year ended December 31,2018.CompetitionThe pharmaceutical industry, in particular, is highly competitive and includes a number of established large and mid-sized companies with greaterfinancial, technical and personnel resources than we have and significantly greater commercial infrastructures than we have. Our market segment alsoincludes several smaller emerging companies whose activities are directly focused on our target markets and areas of expertise. Our products, once approvedfor commercial use, will compete with numerous therapeutic treatments offered by these competitors. While we believe that our products will have certainfavorable features, existing and new treatments may also possess advantages. Additionally, the development of other drug technologies and methods ofdisease prevention are occurring at a rapid pace. These developments may render our products or technologies obsolete or noncompetitive.We believe the primary competitors for HETLIOZ® and Fanapt® are as follows: •For HETLIOZ® in the treatment of Non-24, there are no FDA approved direct competitors. Sedative-Hypnotic treatments for certain sleep relateddisorders include, Ambien® (zolpidem) by Sanofi (including Ambien CR®), Lunesta® (eszopiclone) by Sunovion Pharmaceuticals Inc., Sonata®(zaleplon) by Pfizer Inc., Rozerem® (ramelteon) by Takeda Pharmaceuticals Company Limited, Silenor® (doxepin) by Pernix Therapeutics,Belsomra® (suvorexant) by Merck & Co., Inc., generic products such as zolpidem, trazodone and doxepin, and over-the-counter remedies suchas Benadryl® and Tylenol PM®. The class of melatonin agonists includes Rozerem® (ramelteon) by Takeda Pharmaceuticals Company Limited,Valdoxan® (agomelatine) by Servier, Circadin® (long-acting melatonin) by Neurim Pharmaceuticals Ltd. and the food supplement melatonin.Shift work and excessive sleepiness disorder treatments include Nuvigil® (armodafinil) and Provigil® (modafinil) both by Teva PharmaceuticalIndustries Ltd.•For Fanapt® in the treatment of schizophrenia, the atypical antipsychotics competitors are Risperdal® (risperidone), including the LAIformulation Risperdal Consta® and Invega® (paliperidone), including the LAI formulation Invega® Sustenna®, each by Ortho-McNeil-JanssenPharmaceuticals, Inc., Zyprexa® (olanzapine), including the LAI formulation Zyprexa® RelprevvTM, each by Eli Lilly and Company, Seroquel®and Seroquel XR® (quetiapine) by AstraZeneca PLC, Abilify® (aripiprazole) by Otsuka America Pharmaceutical Inc., Abilify Maintena® (the LAIformulation of Abilify®) by Lundbeck/Otsuka America Pharmaceutical Inc., Geodon® (ziprasidone) by Pfizer Inc., Saphris® (asenapine) byAllergan plc, Latuda® (lurasidone) by Sunovion Pharmaceuticals Inc., Rexulti® (brexpiprazole) by Lundbeck/Otsuka America Pharmaceutical,Inc., AristadaTM (aripiprazole lauroxil) extended-release injectable suspension by Alkermes, Inc., VraylarTM (cariprazine) by TevaPharmaceutical Industries Ltd., and generic clozapine, as well as the typical antipsychotics haloperidol, chlorpromazine, thioridazine, andsulpiride (all of which are generic).Our ability to compete successfully will depend in part on our ability to utilize our pharmacogenetics and pharmacogenomics and drugdevelopment expertise to identify, develop, secure rights to and obtain regulatory approvals for14Table of Contentspromising pharmaceutical products before others are able to develop competitive products. Our ability to compete successfully will also depend on ourability to attract and retain skilled and experienced personnel. Additionally, our ability to compete may be affected because insurers and other third-partypayors in some cases seek to encourage the use of cheaper, generic products, which could make our products less attractive.Government RegulationGovernment authorities in the U.S., at the federal, state and local level, as well as foreign countries and local foreign governments, regulate theresearch, development, testing, manufacture, labeling, promotion, advertising, distribution, sampling, marketing, import and export of our products. Otherthan HETLIOZ® in the U.S. and the E.U. and Fanapt® in the U.S., Israel and Mexico, all of our products will require regulatory approval by governmentagencies prior to commercialization. In particular, human pharmaceutical products are subject to rigorous preclinical and clinical trials and other approvalprocedures of the FDA and similar regulatory authorities in foreign countries. The process of obtaining these approvals and the subsequent compliance withappropriate domestic and foreign laws, rules and regulations require the expenditure of significant time and human and financial resources.United States government regulationFDA approval processIn the U.S., the FDA regulates drugs under the Federal Food, Drug and Cosmetic Act (FDCA), as amended, and implements regulations. If we fail tocomply with the applicable requirements at any time during the product development process, approval process, or after approval, we may become subject toadministrative or judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, withdrawals of approvals, clinicalholds, warning letters, product recalls, product seizures, total or partial suspension of our operations, injunctions, fines, civil penalties or criminalprosecution. Any such sanction could have a material adverse effect on our business.The steps required before a drug may be marketed in the U.S. include: •preclinical laboratory tests, animal studies and formulation studies under Current Good Laboratory Practices (cGLP);•submission to the FDA of an IND, which must become effective before human clinical trials may begin;•execution of adequate and well-controlled clinical trials to establish the safety and efficacy of the drug for each indication for which approval issought;•submission to the FDA of an NDA;•satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance withCurrent Good Manufacturing Practices (cGMP); and•FDA review and approval of the NDA.Preclinical studies generally are conducted in laboratory animals to evaluate the potential safety and activity of a drug. Violation of the FDA’s cGLPregulations can, in some cases, lead to invalidation of the studies, requiring these studies to be replicated. In the U.S., drug developers submit the results ofpreclinical trials, together with manufacturing information and analytical and stability data, to the FDA as part of the IND, which must become effectivebefore clinical trials can begin in the U.S. An IND becomes effective 30 days after receipt by the FDA unless before that time the FDA raises concerns orquestions about issues such as the proposed clinical trials outlined in the IND. In that case, the IND sponsor and the FDA must resolve any outstanding FDAconcerns or questions before clinical trials can proceed. If these concerns or questions are unresolved, the FDA may not allow the clinical trials to commence.Pilot studies generally are conducted in a limited patient population, approximately three to 25 subjects, to determine whether the drug warrantsfurther clinical trials based on preliminary indications of efficacy. These pilot studies may be performed in the U.S. after an IND has become effective oroutside of the U.S. prior to the filing of an IND in the U.S. in accordance with applicable government regulations and institutional procedures.Clinical trials involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators.Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in assessing the safety andthe effectiveness of the drug. Each protocol must be submitted to the FDA as part of the IND prior to beginning the trial.15Table of ContentsTypically, clinical evaluation involves a time-consuming and costly three-Phase sequential process, but the phases may overlap. Each trial must bereviewed, approved and conducted under the auspices of an independent Institutional Review Board, and each trial must include the patient’s informedconsent. •Phase I: refers typically to closely-monitored clinical trials and includes the initial introduction of an investigational new drug into humanpatients or healthy volunteer subjects. Phase I trials are designed to determine the safety, metabolism and pharmacologic actions of a drug inhumans, the potential side effects associated with increasing drug doses and, if possible, to gain early evidence of the drug’s effectiveness. PhaseI trials also include the study of structure-activity relationships and mechanism of action in humans, as well as studies in which investigationalnew drugs are used as research tools to explore biological phenomena or disease processes. During Phase I trials, sufficient information about adrug’s pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid Phase IIstudies. The total number of subjects and patients included in Phase I trials varies, but is generally in the range of 20 to 80 people.•Phase II: refers to controlled clinical trials conducted to evaluate appropriate dosage and the effectiveness of a drug for a particular indication orindications in patients with a disease or condition under study and to determine the common short-term side effects and risks associated with thedrug. These trials are typically well-controlled, closely monitored and conducted in a relatively small number of patients, usually involving nomore than several hundred subjects.•Phase III: refers to expanded controlled and uncontrolled clinical trials. These trials are performed after preliminary evidence suggestingeffectiveness of a drug has been obtained. Phase III trials are intended to gather additional information about the effectiveness and safety that isneeded to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. Phase III trialsusually include several hundred to several thousand subjects.•Phase IV: refers to post-approval studies, when applicable, are conducted following initial approval, typically to gain additional experience anddata from treatment of patients in the intended therapeutic indication.Phase I, II and III testing may not be completed successfully within any specified time period, if at all. The FDA closely monitors the progress of eachof the three phases of clinical trials that are conducted in the U.S. and may, at its discretion, reevaluate, alter, suspend or terminate the testing based upon thedata accumulated to that point and the FDA’s assessment of the risk/benefit ratio to the patient. A clinical program is designed after assessing the causes ofthe disease, the mechanism of action of the active pharmaceutical ingredient of the drug and all clinical and preclinical data of previous trials performed.Typically, the trial design protocols and efficacy endpoints are established in consultation with the FDA. Upon request through a special protocolassessment, the FDA can also provide specific guidance on the acceptability of protocol design for clinical trials. The FDA or we may suspend or terminateclinical trials at any time for various reasons, including a finding that the subjects or patients are being exposed to an unacceptable health risk. The FDA canalso request additional clinical trials be conducted as a condition to drug approval. During all clinical trials, physicians monitor the patients to determineeffectiveness and to observe and report any reactions or other safety risks that may result from use of the drug.Assuming successful completion of the required clinical trials, drug developers submit the results of preclinical studies and clinical trials, togetherwith other detailed information including information on the manufacture and composition of the drug, to the FDA, in the form of an NDA, requestingapproval to market the drug for one or more indications. In most cases, the NDA must be accompanied by a substantial user fee. Under PDUFA-VI, thesubmission of most NDAs is additionally subject to a significant human drug application fee, which is collected at the time of submission. PDUFA-VIeliminated user fees for supplements and establishments. In addition, the sponsor of an approved NDA is also subject to annual program fee. For federal fiscalyear 2019, the submission of an NDA for which clinical data (other than bioavailability or bioequivalence studies) with respect to safety or effectiveness arerequired for approval is subject to an application user fee of $2,588,478. The annual program user fee for fiscal year 2019 is $309,915. The FDA reviews anNDA to determine, among other things, whether a drug is safe and effective for its intended use.The FDA conducts a preliminary review of an NDA generally within 60 calendar days of its receipt and strives to inform the sponsor by the 74th dayafter the FDA’s receipt of the submission to determine whether the application is sufficiently complete before the agency accepts it for filing and conductssubstantive review.Before approving an NDA, the FDA will inspect the facility or facilities where the drug is manufactured. The FDA will not approve the applicationunless cGMP compliance is satisfactory. The FDA will issue an approval letter if it determines that the application, manufacturing process and manufacturingfacilities are acceptable. If the FDA determines that the NDA, manufacturing process or manufacturing facilities are not acceptable, it will issue a completeresponse letter (CRL), in which it16Table of Contentswill outline the deficiencies in the submission and will often request additional testing or information. Notwithstanding the submission of any requestedadditional information, the FDA may ultimately decide that the NDA does not satisfy the regulatory criteria for approval and refuse to approve the NDA.The testing and approval process requires substantial time, effort and financial resources, and each may take several years to complete. The FDA maynot grant approval on a timely basis, or at all. We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals,which could delay or preclude us from marketing our products. Furthermore, the FDA may prevent a drug developer from marketing a drug under a label forits desired indications or place other conditions on distribution as a condition of any approvals, which may impair commercialization of the drug. Afterapproval, some types of changes to the approved drug, such as adding new indications, manufacturing changes and additional labeling claims, are subject tofurther FDA review and approval. Similar regulatory procedures must also be followed within countries outside the U.S.If the FDA approves the NDA, the drug becomes available for physicians to prescribe in the U.S. After approval of our products, we have to complywith a number of post-approval requirements, including delivering periodic reports to the FDA, submitting descriptions of any adverse reactions reported,and complying with drug sampling and distribution requirements. We also are required to provide updated safety and efficacy information and to complywith requirements concerning advertising and promotional labeling. Also, our quality control and manufacturing procedures must continue to conform tocGMP after approval. Drug manufacturers and their subcontractors are required to register their facilities and are subject to periodic unannounced inspectionsby the FDA to assess compliance with cGMP which imposes certain procedural and documentation requirements relating to quality assurance and qualitycontrol. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliancewith cGMP and other aspects of regulatory compliance. The FDA may require post market testing and surveillance to monitor the drug’s safety or efficacy,including additional studies, known as Phase IV trials, to evaluate long-term effects.In addition to studies requested by the FDA after approval, we may have to conduct other trials and studies to explore use of the approved productfor treatment of new indications, which require FDA approval. The purpose of these trials and studies is to broaden the application and use of the product andits acceptance in the medical community.We use, and will continue to use, third-party manufacturers to produce our products in clinical and commercial quantities. Future FDA inspectionsmay identify compliance issues at our facilities or at the facilities of our contract manufacturers that may disrupt production or distribution, or requiresubstantial resources to correct. In addition, discovery of problems with a product or the failure to comply with requirements may result in restrictions on aproduct, manufacturer or holder of an approved NDA, including withdrawal or recall of the product from the market or other voluntary or FDA-initiatedaction that could delay further marketing. Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling,including the addition of new warnings and contraindications.In September 2007, the Food and Drug Administration Amendments Act (FDAAA), was enacted into law, amending the FDCA and the Public HealthService Act. The FDAAA made a number of substantive and incremental changes to the review and approval processes in ways that could make it moredifficult or costly to obtain approval for new pharmaceutical products, or to produce, market and distribute existing pharmaceutical products. Mostsignificantly, the law changed the FDA’s handling of postmarked drug product safety issues by giving the FDA authority to require post approval studies orclinical trials, to request that safety information be provided in labeling, or to require an NDA applicant to submit and execute a Risk Evaluation andMitigation Strategy (REMS).The FDAAA made certain changes to the user fee provisions to permit the use of user fee revenue to fund the FDA’s drug product safety activitiesand the review of Direct-to-Consumer advertisements. The Food and Drug Administration Safety and Innovation Act of 2012, which became effective inOctober 2012, reauthorized the authority of the FDA to collect user fees to fund the FDA’s review activities.In addition, new government requirements may be established that could delay or prevent regulatory approval of our products under development.The Hatch-Waxman ActIn seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s drug.Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with TherapeuticEquivalence Evaluations, commonly known as the “Orange Book.” Drugs listed in the Orange Book can, in turn be cited by potential competitors in supportof approval of an abbreviated17Table of Contentsnew drug application (ANDA). An ANDA provides for marketing of a drug that has the same active ingredients in the same strengths and dosage form as thelisted drug and has been shown through bioequivalence testing to be therapeutically equivalent to the listed drug. ANDA applicants are not required toconduct or submit results of preclinical or clinical tests to prove the safety or effectiveness of their drug, other than the requirement for bioequivalencetesting. Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug, and can often be substituted by pharmacists underprescriptions written for the original listed drug.The ANDA applicant is required to certify to the FDA concerning any patents listed for the approved drug in the Orange Book. Specifically, theapplicant must certify that: (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired, butwill expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new drug. Acertification that the new drug will not infringe the already approved drug’s listed patents or that such patents are invalid is called a Paragraph IVcertification. If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming thereferenced drug have expired.If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification tothe NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringementlawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IVcertification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit or adecision in the infringement case that is favorable to the ANDA applicant.The ANDA application also will not be approved until any non-patent exclusivity, such as exclusivity for obtaining approval of a NCE, listed in theOrange Book for the referenced drug has expired. The U.S. Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known as the“Hatch-Waxman Act,” provides a period of five years following approval of a drug containing no previously approved active ingredients, during whichANDAs for generic versions of those drugs cannot be submitted unless the submission contains a Paragraph IV challenge to a listed patent, in which case thesubmission may be made four years following the original drug approval. Federal law provides for a period of three years of exclusivity following approval ofa listed drug that contains previously approved active ingredients but is approved in a new dosage form, route of administration or combination, or for a newuse, the approval of which was required to be supported by new clinical trials conducted by or for the sponsor, during which FDA cannot grant effectiveapproval of an ANDA based on that listed drug.Foreign regulationWhether or not we obtain FDA approval for a product, we must obtain approval by the comparable regulatory authorities of foreign countries beforewe can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country, and the time may belonger or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing andreimbursement also vary greatly from country to country. Although governed by the applicable country, clinical trials conducted outside of the U.S. typicallyare administered with the three-Phase sequential process that is discussed above under “United States government regulation.” However, the foreignequivalent of an IND is not a prerequisite to performing pilot studies or Phase I clinical trials.Under E.U. regulatory systems, we may submit Marketing Authorization Applications (MAAs) either under a centralized or decentralized procedure.The centralized procedure, which is available for drugs produced by biotechnology or which are highly innovative, provides for the grant of a singlemarketing authorization that is valid for all E.U. member states. This authorization is a marketing authorization approval. The decentralized procedureprovides for mutual recognition of national approval decisions. Under this procedure, the holder of a national marketing authorization may submit anapplication to the remaining member states. Within 90 days of receiving the applications and assessment report, each member state must decide whether torecognize approval. This procedure is referred to as the mutual recognition procedure.In addition, regulatory approval of prices is required in most countries other than the U.S. We face the risk that the resulting prices would beinsufficient to generate an acceptable return to us.Pharmaceutical Coverage, Pricing and ReimbursementSignificant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities. Salesof products will depend, in part, on the extent to which the costs of the products will be covered by third-party payors, including government health programsin the United States such as Medicare and Medicaid, commercial18Table of Contentshealth insurers and managed care organizations. The process for determining whether a payor will provide coverage for a product may be separate from theprocess for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors are increasinglychallenging the prices charged, examining the medical necessity, and reviewing the cost-effectiveness of medical products and services and imposingcontrols to manage costs. Third-party payors may also limit coverage to specific products on an approved list, or formulary, which might not include all ofthe approved products for a particular indication.In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensivepharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtainFDA or other comparable regulatory approvals. A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursementrate will be approved. Third-party reimbursement may not be sufficient to maintain price levels high enough to realize an appropriate return on investment inproduct development.The containment of healthcare costs also has become a priority of federal, state and foreign governments and the prices of drugs have been a focus inthis effort. Governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursementand requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies injurisdictions with existing controls and measures, could further limit a company’s revenue generated from the sale of any approved products. Coveragepolicies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or moreproducts for which a company or its collaborators receive marketing approval, less favorable coverage policies and reimbursement rates may be implementedin the future. In the E.U., pricing and reimbursement schemes vary widely from country to country. Some countries provide that drug products may bemarketed only after a reimbursement price has been agreed. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular drug candidate to currently available therapies, or so called health technology assessments, in order to obtain reimbursement orpricing approval. For example, the E.U. provides options for its member states to restrict the range of drug products for which their national health insurancesystems provide reimbursement and to control the prices of medicinal products for human use. E.U. member states may approve a specific price for a drugproduct or may instead adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market. Other memberstates allow companies to fix their own prices for drug products, but monitor and control company profits. The downward pressure on health care costs ingeneral, particularly prescription drugs, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition,in some countries, cross-border imports from low-priced markets exert competitive pressure that may reduce pricing within a country. Any country that hasprice controls or reimbursement limitations for drug products may not allow favorable reimbursement and pricing arrangements.A primary trend in the U.S. healthcare industry and elsewhere is cost containment. There have been a number of federal and state proposals duringthe last several years regarding the pricing of pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for drugs and othermedical products, government control and other changes to the healthcare system in the U.S.By way of example, the U.S. and state governments continue to propose and pass legislation designed to reduce the cost of healthcare. In March2010, the U.S. Congress enacted the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability ReconciliationAct of 2010 (together, PPACA), which, among other things, includes changes to the coverage and payment for products under government health careprograms. Among the provisions of the PPACA of importance to potential drug candidates are:•an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportionedamong these entities according to their market share in certain government healthcare programs, although this fee would not apply to sales ofcertain products approved exclusively for orphan indications;•expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individualswith income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;•expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded andgeneric drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid drug rebates onoutpatient prescription drug prices and extending rebate liability to prescriptions for individuals enrolled in Medicare Advantage plans;19Table of Contents•addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs thatare inhaled, infused, instilled, implanted or injected;•expanded the types of entities eligible for the 340B drug discount program;•established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50% point‑of‑sale‑discount off thenegotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’outpatient drugs to be covered under Medicare Part D. Public Law No. 115-123, also known as the Bipartisan Budget Act of 2018 enacted onFebruary 9, 2018 increased the manufacturer discount from 50% to 70% effective in 2019 for applicable drugs;•established a new Patient‑Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinicaleffectiveness research, along with funding for such research;•established the Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to the Medicare program toreduce expenditures by the program that could result in reduced payments for prescription drugs. However, the IPAB implementation has beennot been clearly defined. The PPACA provided that under certain circumstances, IPAB recommendations will become law unless Congressenacts legislation that will achieve the same or greater Medicare cost savings; and•established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lowerMedicare and Medicaid spending, potentially including prescription drug spending. Funding has been allocated to support the mission of theCenter for Medicare and Medicaid Innovation from 2011 to 2019. Other legislative changes have been proposed and adopted since the PPACAwas enacted. These changes include the Budget Control Act of 2011, which, among other things, led to aggregate reductions to Medicarepayments to providers of up to 2% per fiscal year that started in 2013 and will stay in effect through 2024 unless additional congressionalaction is taken, and the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several types ofproviders and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. Thesenew laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any ofour product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed orused. Further, there have been several recent U.S. congressional inquiries and proposed state and federal legislation designed to, among otherthings, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs ofdrugs under Medicare and reform government program reimbursement methodologies for drug products.These healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions inMedicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price for anyapproved product and/or the level of reimbursement physicians receive for administering any approved product. Reductions in reimbursement levels maynegatively impact the prices or the frequency with which products are prescribed or administered. Any reduction in reimbursement from Medicare or othergovernment programs may result in a similar reduction in payments from private payors. Since enactment of the PPACA, there have been numerous legalchallenges and congressional actions to repeal and replace provisions of the law. Various pieces of legislation have been proposed and/or passed by each ofthe chambers of Congress to achieve those objectives, but to date, few of these measures have been implemented.The current presidential administration has also taken executive actions to undermine or delay implementation of the PPACA. In January 2017, thePresident signed an Executive Order directing federal agencies with authorities and responsibilities under the PPACA to waive, defer, grant exemptions from,or delay the implementation of any provision of the PPACA that would impose a fiscal or regulatory burden on states, individuals, healthcare providers,health insurers, or manufacturers of pharmaceuticals or medical devices. In October 2017, the President signed a second Executive Order allowing for the useof association health plans and short-term health insurance, which may provide fewer health benefits than the plans sold through the PPACA exchanges. Atthe same time, the Administration announced that it will discontinue the payment of cost-sharing reduction (CSR) payments to insurance companies untilCongress approves the appropriation of funds for such CSR payments. The loss of the CSR payments is expected to increase premiums on certain policiesissued by qualified health plans under the PPACA.More recently, with enactment of the Tax Cuts and Jobs Act of 2017 (TCJA), which was signed by the President on December 22, 2017, Congressrepealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effectiveon January 1, 2019. According to the Congressional Budget Office, the repeal of the individual mandate will cause 13 million fewer Americans to be insuredin 2027 and premiums in20Table of Contentsinsurance markets may rise. Additionally, on January 22, 2018, the President signed a continuing resolution on appropriations for fiscal year 2018 thatdelayed the implementation of certain PPACA-mandated fees, including the so-called “Cadillac” tax on certain high cost employer-sponsored insuranceplans, the annual fee imposed on certain health insurance providers based on market share, and the medical device excise tax on non-exempt medicaldevices. Further, there have been several recent U.S. congressional inquiries and proposed federal and proposed and enacted state legislation designed to,among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs ofdrugs under Medicare and reform government program reimbursement methodologies for drug products. At the federal level, Congress and the currentpresidential administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs. At the statelevel, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biologicalproduct pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure andtransparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health careauthorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will beincluded in their prescription drug and other health care programs. These measures could reduce the ultimate demand for our products, once approved, or putpressure on our product pricing.EmployeesWe had 270 full-time employees as of December 31, 2018, compared with 273 employees as of December 31, 2017. None of our employees arerepresented by a labor union. We have not experienced any work stoppages and consider our employee relations to be good.Corporate InformationWe were incorporated in Delaware in 2002. Our principal executive offices are located at 2200 Pennsylvania Avenue NW, Suite 300E, WashingtonD.C. 20037, and our telephone number is (202) 734-3400. Our website address is www.vandapharma.com and the information contained in, or that can beaccessed through, our website is not part of this annual report and should not be considered part of this annual report.Available InformationWe file annual, quarterly, and current reports, proxy statements, and other documents with the Securities and Exchange Commission (SEC) under theSecurities Exchange Act of 1934 (Exchange Act). The SEC maintains a website at www.sec.gov that contains reports, proxy and information statements, andother information regarding issuers, including us, that file electronically with the SEC.We also make available free of charge on our Internet website at www.vandapharma.com our annual reports on Form 10-K, quarterly reports on Form10-Q, current reports on Form 8-K, and, if applicable, amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act assoon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.Our code of ethics, other corporate policies and procedures, and the charters of our Audit Committee, Compensation Committee andNominating/Corporate Governance Committee are available through our Internet website at www.vandapharma.com.ITEM 1A.RISK FACTORSOur business, financial condition and operating results can be affected by a number of factors, whether currently known or unknown, includingbut not limited to those described below, any one or more of which could, directly or indirectly, cause our actual operating results and financial conditionto vary materially from past, or anticipated future, operating results and financial condition. Any of these factors, in whole or in part, could materially andadversely affect our business, financial condition, operating results and the price of our common stock.The following discussion of risk factors contains forward-looking statements. These risk factors may be important to understanding any statementin this annual report on Form 10-K or elsewhere. The following information should be read in21Table of Contentsconjunction with the consolidated financial statements and related notes in Part I, Item 1, Financial Statements and Part I, Item 2, Management’s,Discussion and Analysis of Financial Condition and Results of Operations.Because of the following factors, as well as other factors affecting our financial condition and operating results, past financial performanceshould not be considered to be a reliable indicator of future performance, and investors should not use historical trends to anticipate results or trends infuture periods.Risks related to our business and industryWe are dependent on the commercial success of HETLIOZ® and Fanapt®.Our future success is currently substantially dependent upon the commercial success of HETLIOZ® for the treatment of Non-24-Hour Sleep-WakeDisorder (Non-24) and Fanapt® for the treatment of schizophrenia.In January 2014, the U.S. Food and Drug Administration (FDA) approved our New Drug Application (NDA) for HETLIOZ® for the treatment of Non-24 and in April 2014, we commenced the U.S. commercial launch of HETLIOZ®. In July 2015, the European Commission (EC) granted centralized marketingauthorization with unified labeling for HETLIOZ® for the treatment of Non-24 in totally blind adults, and in August 2016 we commenced the commerciallaunch of HETLIOZ® in Germany. This authorization is valid in the 28 countries that are members of the European Union (E.U.), as well as EuropeanEconomic Area members Iceland, Liechtenstein and Norway.In the fourth quarter of 2014, we acquired the U.S. commercial rights to Fanapt®, and began selling, marketing and distributing Fanapt® in the U.S.Our ability to generate significant product revenue from sales of HETLIOZ® and Fanapt®, both in the U.S. and abroad, in the near term will dependon, among other things, our ability to: •defend our patents and intellectual property from generic competition;•maintain commercial manufacturing arrangements with third-party manufacturers;•produce, through a validated process, sufficiently large quantities of inventory of our products to meet demand;•continue to maintain and grow a wide variety of internal sales, distribution and marketing capabilities sufficient to sustain growth in sales of ourproducts;•gain broad acceptance of our products from physicians, health care payors, patients, pharmacists and the medical community;•properly price and obtain adequate coverage and reimbursement of these products by governmental authorities, private health insurers,managed care organizations and other third-party payors;•maintain compliance with ongoing labeling, packaging, storage, advertising, promotion, recordkeeping, safety and other post-marketrequirements;•obtain regulatory approval to expand the labeling of our approved products for additional indications;•obtain regulatory approval for HETLIOZ® or Fanapt® in additional countries;•adequately protect against and effectively respond to any claims by holders of patents and other intellectual property rights that our productsinfringe their rights; and•adequately protect against and effectively respond to any unanticipated adverse effects or unfavorable publicity that develops in respect to ourproducts, as well as the emergence of new or existing competitive products, which may be proven to be more clinically effective and cost-effective.We expect to continue to incur significant expenses and to utilize a substantial portion of our cash resources as we continue the commercializationof HETLIOZ® and Fanapt®, evaluate foreign market opportunities for HETLIOZ® and Fanapt® and continue to grow our operational capabilities, bothdomestically and abroad. This activity represents a significant investment in the commercial success of HETLIOZ® and Fanapt®, which is uncertain.If our continued commercial efforts are not successful with respect to HETLIOZ® and Fanapt® in the U.S., Europe or other jurisdictions in whichthese products may be approved for sale, our ability to generate increased product sales revenue may be jeopardized and, consequently, our business may beseriously harmed.22Table of ContentsThe cost of growing and maintaining a sales, marketing and distribution organization may exceed its cost effectiveness. If we fail to continue todevelop sales, marketing and distribution capabilities, if sales efforts are not effective or if costs of developing sales, marketing and distribution capabilitiesexceed their cost effectiveness, our business, results of operations and financial condition could be materially adversely affected.Growth of HETLIOZ® and Fanapt® may be slow or limited for a variety of reasons including competing products or unanticipated safety issues. Ifeither HETLIOZ® or Fanapt® is not successful in gaining broad commercial acceptance, our business would be harmed.Any increase in sales of HETLIOZ® and Fanapt® will be dependent on several factors, including our ability to educate physicians and to increasephysician awareness of the benefits of our products relative to competing products. The degree of further market acceptance of any of our products or marketacceptance of approved product candidates among physicians, patients, health care payors and the medical community will depend on a number of factors,including but not limited to: •acceptable evidence of safety and efficacy;•relative convenience and ease of administration;•the prevalence and severity of any adverse side effects;•availability of alternative treatments; and•pricing and cost effectiveness.In addition, HETLIOZ® and Fanapt® are subject to continual review by the FDA, and we cannot assure that newly discovered or reported safetyissues will not arise. With the use of any newly marketed drug by a wider patient population, serious adverse events may occur from time to time that initiallydo not appear to relate to the drug itself. Any safety issues could cause us to suspend or cease marketing of our approved products, cause us to modify how wemarket our approved products, subject us to substantial liabilities and adversely affect our revenues and financial condition. In the event of a withdrawal ofeither HETLIOZ® or Fanapt® from the market, our revenues would decline significantly and our business would be seriously harmed.If the FDA does not accept for filing the NDAs that we may submit for tradipitant for the treatment of chronic pruritus in atopic dermatitis and thetreatment of gastroparesis, regulatory authorities determine that our clinical trial results for tradipitant for the treatment of chronic pruritus in atopicdermatitis or the treatment of gastroparesis do not demonstrate adequate safety and efficacy, or the FDA does not approve an applicable PDUFA-VI date,continued development of tradipitant will be significantly delayed or terminated, our business will be significantly harmed, and the market price of ourstock could decline.We announced the results in September 2017 from a randomized Phase II clinical study of tradipitant as a monotherapy in the treatment of chronicpruritus in patients with atopic dermatitis. Tradipitant was shown to improve the intensity of the worst itch patients experienced, as well as atopic dermatitisdisease severity.We announced results in December 2018 from a randomized clinical study (2301) of tradipitant as a monotherapy in the treatment of gastroparesis.Tradipitant met the primary endpoint of the study of change in nausea score as measured by patient daily diaries and also met the related endpoint ofimprovement in the number of nausea free days. Tradipitant also showed significant improvement in most of the secondary endpoints studied, including theseveral key scales reflecting overall gastroparesis symptoms, specifically GCSI; PAGI-SYM; CGI-S; PGI-C.If the results of our ongoing Phase III clinical study of tradipitant for the treatment of chronic pruritus in atopic dermatitis and/or our planned PhaseIII clinical study of tradipitant for the treatment of gastroparesis are positive, we will likely submit an NDA with the FDA for these indications. Any adversedevelopments or results or perceived adverse developments or results with respect to our pre-NDA meeting with the FDA, our regulatory submission or thetradipitant clinical programs in either or both indications will significantly harm our business and could cause the market price of our stock to decline.Examples of such adverse developments include, but are not limited to:•the FDA determining that additional clinical studies are required with respect to the tradipitant for the treatment of chronic pruritus in atopicdermatitis and/or the treatment of gastroparesis;•safety, efficacy or other concerns arising from clinical or non-clinical studies in these programs; or•the FDA determining that the tradipitant clinical trial programs raise safety concerns or do not demonstrate adequate efficacy.23Table of ContentsIn April 2018, we submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) period for patients who hadcompleted the tradipitant Phase II clinical study (2301) in gastroparesis. In May 2018, based on feedback from the FDA, we amended the protocol limitingthe duration of treatment in the 2301 study to a total of three months, while continuing to seek further dialogue with the FDA on extending the studyduration to 52-weeks. As a part of this negotiation process, in September 2018, we submitted a new follow-on 52-week OLE protocol to the FDA (2302) forpatients who had completed the 2301 study. While waiting for further feedback, no patients were ever enrolled in any study beyond 12 weeks. On December19, 2018, the FDA imposed a partial clinical hold (PCH) on the two proposed studies, stating that we are required first to conduct additional chronic toxicitystudies in canines, monkeys or minipigs before allowing patients access in any clinical protocol beyond 12 weeks. The PCH was not based on any safety orefficacy data related to tradipitant. Rather, the FDA informed us that these additional toxicity studies are required by a guidance document. We do not expectthe PCH to have any material impact on our ongoing clinical studies in atopic dermatitis and motion sickness or the planned Phase III study in gastroparesis.At present, the PCH has not had any impact on the potential timing of an NDA filing or approval for these indications. We will continually reassess thissituation as events unfold.On February 5, 2019, we filed a lawsuit against the FDA in the United States District Court for the District of Columbia, challenging the FDA’s legalauthority to issue the PCH, and seeking an order to set it aside. On February 14, 2019, the FDA filed a Motion for Voluntary Remand to the Agency and for aStay of the Case. We intend to continue vigorously pursuing our interests in the matter (see Part I, Item 3, Legal Proceedings of this annual report on Form10-K for additional information).Even if our lawsuit challenging the FDA’s authority to issue the PCH is successful, there can be no assurances that the FDA will not attempt toimpose a clinical hold or PCH on other grounds. While we believe we have a strong legal basis, this litigation is subject to uncertainties and we may notprevail. Because the PCH could, however, impede our ability to conduct longer term studies of tradipitant, whether the PCH impacts the timing orapprovability of NDA filings with the FDA for any indication will depend on a number of factors, including whether the PCH is resolved through the lawsuitdescribed above, whether we resolve the PCH out of court through discussions with the FDA, and, in addition to the non-clinical animal studies, whether theFDA considers the clinical trials that we conduct to be sufficient. A delay in filing, or FDA delay or denial of approval, of NDA filings for tradipitant for thetreatment of chronic pruritus in atopic dermatitis, gastroparesis or motion sickness could materially adversely impact our business.If the FDA does not approve our supplemental New Drug Application (sNDA) for tasimelteon for the treatment jet lag disorder, or does not agree to anacceptable regulatory path forward for tasimelteon for the treatment of Smith-Magenis Syndrome (SMS) or continued development of tasimelteon for thetreatment of either jet lag disorder or SMS is significantly delayed or terminated, our business will be significantly harmed, and the market price of ourstock could decline.In December 2018, we announced that the FDA had accepted the HETLIOZ® sNDA for the treatment of jet lag disorder with a PDUFA-VI targetaction date of August 16, 2019. We expect to meet with the FDA by mid-2019 to confirm the regulatory path forward for HETLIOZ® in the treatment of SMSand discuss the further development of HETLIOZ® for the treatment of sleep disorders in patients with neurodevelopmental disorders. Any adversedevelopments or results or perceived adverse developments or results with respect to our regulatory submission for jet lag disorder or our meeting with theFDA to determine the regulatory path forward for HETLIOZ® in the treatment of SMS will significantly harm our business and could cause the market price ofour stock to decline. Examples of such adverse developments include, but are not limited to:•the FDA determining that additional clinical studies are required with respect to either the SMS or jet lag disorder program;•safety, efficacy or other concerns arising from clinical or non-clinical studies in either the SMS or jet lag disorder program, or the manufacturingprocesses or facilities used for either the SMS or jet lag disorder programs; or•the FDA determining that either the SMS or jet lag disorder program raises safety concerns or does not demonstrate adequate efficacy.We may enter into third party collaborations from time to time in order to develop and commercialize our products. If we are unable to identify orenter into an agreement with any material third-party collaborator, if our collaborations with any such third-party are not commercially successful or ifour agreement with any such third-party is terminated or allowed to expire, we could be adversely affected financially or our business reputation could beharmed.Our business strategy includes entering into collaborations with corporate collaborators for the commercialization of HETLIOZ®, Fanapt® and ourother products. While we are not currently party to any material commercial collaborative arrangements, areas in which we may potentially enter into third-party collaboration arrangements include joint sales and marketing arrangements for sales and marketing in certain E.U. countries and elsewhere outside ofthe U.S., and future product24Table of Contentsdevelopment arrangements. If we are unable to identify or enter into an agreement with any material third-party collaborator, this could result in an adverseeffect on our business, results of operations or financial condition. Any arrangements we do enter into may not be scientifically or commercially successful.The termination of any of these arrangements might adversely affect our ability to develop, commercialize and market our products.The success of our collaboration arrangements will depend heavily on the efforts and activities of our collaborators. Our collaborators will havesignificant discretion in determining the efforts and resources that they will apply to these collaborations. We expect that the risks which we face inconnection with these future collaborations will include the following:•our collaboration agreements are expected to be for fixed terms and subject to termination under various circumstances, including, in manycases, on short notice without cause;•our collaborators may develop and commercialize, either alone or with others, products and services that are similar to or competitive with ourproducts which are the subject of their collaboration with us; and•our collaborators may change the focus of their commercialization efforts.In recent years there have been a significant number of mergers and consolidations in the pharmaceutical and biotechnology industries, some ofwhich have resulted in the participant companies reevaluating and shifting the focus of their business following the completion of these transactions. Theability of our products to reach their potential could be limited if any of our future collaborators decreases or fails to increase spending relating to suchproducts.Collaborations with pharmaceutical companies and other third-parties often are terminated or allowed to expire by the other party. With respect toour future collaborations, any such termination or expiration could adversely affect us financially as well as harm our business reputation.Even after we obtain regulatory approvals of a product, acceptance of the product in the marketplace is uncertain and failure to achieve commercialacceptance will prevent or delay our ability to generate significant revenue from such product.Even after obtaining regulatory approvals for the sale of our products, the commercial success of these products will depend, among other things, ontheir acceptance by physicians, patients, third-party payors and other members of the medical community as therapeutic and cost-effective alternatives tocompeting products and treatments. The degree of market acceptance of any product will depend on a number of factors, including the demonstration of itssafety and efficacy, its cost-effectiveness, its potential advantages over other therapies, the reimbursement policies of government and third-party payors withrespect to such product, our ability to attract and maintain corporate partners, including pharmaceutical companies, to assist in commercializing our products,receipt of regulatory clearance of marketing claims for the uses that we are developing and the effectiveness of our marketing and distribution capabilities. Ifour approved products fail to gain market acceptance or do not become widely accepted by physicians, patients, third-party payors and other members of themedical community, it is unlikely that we will ever become profitable on a sustained basis or achieve significant revenues.We rely and will continue to rely on outsourcing arrangements for many of our activities, including clinical development and supply of HETLIOZ®,Fanapt® and our other products.As of December 31, 2018, we had 270 full-time employees. We rely on outsourcing arrangements for a significant portion of our activities, includingdistribution, clinical research and development, data collection and analysis and manufacturing, as well as for certain functions as a public company. Wehave limited control over these third parties and we cannot guarantee that they will perform their obligations in an effective and timely manner.Disruptions to our HETLIOZ® or Fanapt® supply chains could materially affect our level of success in commercializing HETLIOZ® or Fanapt®,thereby reducing our future earnings and prospects.A loss or disruption with any one of our manufacturers or suppliers could disrupt the supply of HETLIOZ® or Fanapt®, possibly for a significant timeperiod, and we may not have sufficient inventories to maintain supply before the manufacturer or supplier could be replaced or the disruption is resolved. Inaddition, marketed drugs and their contract manufacturing organizations are subject to continual review, including review and approval by regulatoryauthorities of their manufacturing facilities and the manufacturing processes, which can result in delays in the regulatory approval process and/orcommercialization. Introducing a replacement or backup manufacturer or supplier for HETLIOZ® or Fanapt® requires a lengthy regulatory and commercialprocess and there can be no guarantee that we could obtain necessary regulatory approvals in a timely fashion or at all. In addition, it is difficult to identifyand select qualified suppliers and manufacturers with the necessary25Table of Contentstechnical capabilities, and establishing new supply and manufacturing sources involves a lengthy and technical engineering process.Failure to comply with government regulations regarding the sale and marketing of our products could harm our business.Pharmaceutical companies are subject to extensive government regulation and oversight by government authorities in countries in which they dobusiness. As a result, we may become subject to governmental actions which could materially and adversely affect our business, results of operations andfinancial condition, certain of which are described below.Pharmaceutical Pricing and ReimbursementIn U.S. markets, our ability to commercialize our products successfully, and to attract commercialization partners for our products, should we chooseto do so, depends in significant part on the availability of adequate financial coverage and reimbursement from third-party payors, including, in the U.S.,governmental payors such as the Medicare and Medicaid programs, managed care organizations, and private health insurers.We participate in the Medicaid Drug Rebate Program for both HETLIOZ® and Fanapt®. Under the Medicaid Drug Rebate Program, we are required topay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaidprogram as a condition of having our drugs eligible for coverage under Medicaid and Medicare Part B. Those rebates are based on pricing data that arereported by us on a monthly and quarterly basis to the Centers for Medicare & Medicaid Services (CMS). Federal law requires that any company thatparticipates in the Medicaid Drug Rebate Program also participate in the Public Health Service’s 340B drug pricing discount program (340B program), inorder for the manufacturer’s drugs to be eligible for coverage under Medicaid and Medicare Part B. The 340B program requires participating manufacturers toagree to charge statutorily-defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered outpatient drugs. The ceiling pricecan represent a significant discount and is based on the pricing data reporting to the Medicaid Drug Rebate Program.The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act of 2010 (together,PPACA) expanded the 340B program to include additional entity types: certain free-standing cancer hospitals, critical access hospitals, rural referral centersand sole community hospitals, each as defined by PPACA. PPACA exempts drugs designated under section 526 of the FDC Act as “orphan drugs” from theceiling price requirements for these newly-eligible entities.PPACA also obligates the Health Resources and Services Administration (HRSA) to create regulations and processes to improve the integrity of the340B program and to update the agreement that manufacturers must sign to participate in the 340B program. HRSA issued a final regulation in January of2017 regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowingly and intentionallyovercharge covered entities, although that regulation has been withdrawn and is not currently applicable. The withdrawn final regulation regarding the 340Bprogram included a requirement that a manufacturer calculate the 340B ceiling price on a quarterly basis, the requirement that a manufacturer charge $0.01per unit of measure if the 340B ceiling price calculation results in a ceiling price that equals zero (penny pricing), the methodology manufacturers must usewhen estimating the ceiling price for a new covered outpatient drug, an explanation of how a civil monetary penalty (CMP) would be imposed on amanufacturer that knowingly and intentionally overcharges a covered entity; and an explanation of what would constitute an instance of overcharging totrigger a CMP. HRSA recently issued a proposed regulation regarding an administrative dispute resolution process for the 340B program. Any finalregulations and guidance could affect our obligations under the 340B program in ways we cannot anticipate. In addition, legislation may be introduced that,if passed, would further expand the 340B program to additional covered entities or otherwise expand the 340B program.Federal law also requires that for a drug manufacturer’s products to be eligible for coverage under the Medicaid and Medicare Part B programs and tobe purchased by certain federal agencies and grantees, the manufacturer must participate in the Department of Veterans Affairs Federal Supply Schedule(FSS), pricing program, established by Section 603 of the Veterans Health Care Act of 1992. Manufacturers that participate in the FSS pricing program mustlist their covered (innovator and authorized generic) drugs on an FSS contract and charge no more than Federal Ceiling Price (FCP), to the Department ofVeterans Affairs, Department of Defense, Public Health Service, and Coast Guard when those agencies purchase from the FSS contract or a depot contract.FCP is calculated based on non-federal average manufacturer price data, which manufacturers must submit quarterly and annually. In addition, because ourproducts are available in the retail and specialty pharmacy setting, we are required to provide rebates to the Department of Defense for prescriptionsdispensed to Tricare beneficiaries from Tricare retail network pharmacies under the Tricare Retail Refund Program. To the extent we choose to participate inthese26Table of Contentsgovernment healthcare programs for our current and future products, these and other requirements may affect our ability to profitably sell any product forwhich we obtain marketing approval.Pricing and rebate calculations vary among products and programs. The calculations are complex and will often be subject to interpretation by us,governmental or regulatory agencies and the courts. If we become aware that our reporting of pricing data for a prior quarter was incorrect, we will beobligated to resubmit the corrected data. For the Medicaid Drug Rebate Program, corrected data must be submitted for a period not to exceed 12 quarters fromthe quarter in which the data originally were due. Such restatements and recalculations increase our costs for complying with the laws and regulationsgoverning the Medicaid Drug Rebate Program and other governmental pricing programs.We may be liable for errors associated with our submission of pricing data. If we are found to have knowingly submitted false pricing data to theMedicaid program or the FSS pricing program, we may be liable for civil monetary penalties in the amount of up to $100,000 per item of false information.Our failure to submit pricing data to the Medicaid program or the FSS pricing program on a timely basis could result in a civil monetary penalty of $10,000per day for each day the information is late. Such failure also could be grounds for CMS to terminate our Medicaid drug rebate agreement, which is theagreement under which we would participate in the Medicaid Drug Rebate Program. In the event that CMS terminates our rebate agreement, our products mayno longer be eligible for coverage under Medicaid or Medicare Part B. There can be no assurance that our submissions will not be found to be incomplete orincorrect.Third-party payors decide which drugs they will cover and establish reimbursement and co-pay levels. Third-party payors are increasinglychallenging the prices charged for medical products and services and examining their cost effectiveness, in addition to their safety and efficacy. We may needto conduct expensive pharmacoeconomic studies in order to demonstrate the cost effectiveness of our products. Even with such studies, any of our productsthat are commercialized may be considered less cost-effective than other products, and third-party payors may not provide coverage and reimbursement, inwhole or in part, for our products.Political, economic and regulatory influences are subjecting the healthcare industry in the U.S. to fundamental changes. There have been, and weexpect there will continue to be, legislative and regulatory proposals to change the healthcare system and reimbursement systems in ways that could impactour ability to profitably sell commercialized products.Payors also are increasingly considering new metrics as the basis for reimbursement rates. It is difficult to project the impact of these evolvingreimbursement mechanics on the willingness of payors to cover any of our commercialized products.In addition, we anticipate that a significant portion of our revenue from sales of commercialized products will be obtained through governmentpayors, including Medicare and Medicaid. Any failure to obtain eligibility for coverage under those programs for products we are able to commercializewould have a material adverse effect on revenues and royalties from sales of such products.Interactions with Healthcare ProvidersPhysicians and other healthcare providers often play a primary role in the recommendation and prescription of pharmaceutical products.Manufacturers of branded prescription drugs are subject to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrainthe business or financial arrangements and relationships through which manufacturers market, sell and distribute the products for which they obtainmarketing approval. Some of the laws and regulations that may affect our ability to operate are described below.Anti-Kickback LawsThe federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting, or receiving remuneration,directly or indirectly, in cash or in kind, to induce or reward the purchasing, leasing, ordering or arranging for or recommending the purchase, lease, or orderof any health care item or service reimbursable under federal healthcare programs such as Medicare and Medicaid. The term “remuneration” has been broadlyinterpreted to include anything of value, and the government can establish a violation of the Anti-Kickback Statute without proving that a person or entityhad actual knowledge of the law or specific intent to violate it. This statute has been interpreted to apply to arrangements between pharmaceuticalmanufacturers on the one hand and prescribers, purchasers, patients, and formulary managers on the other. There are a number of statutory exceptions andregulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions, however, the exceptions and safe harbors aredrawn narrowly. Failure to meet all of the requirements of a particular statutory exception or regulatory safe harbor does not make the conduct per se illegalunder the Anti-Kickback Statute, but the legality of the arrangement will be evaluated on a case-by-case basis based on the totality of the facts andcircumstances. A number of states also have anti-kickback laws that establish similar prohibitions that may apply to27Table of Contentsitems or services reimbursed by government programs, as well as any third-party payors, including commercial payors. Violations of the Anti-KickbackStatute are punishable by imprisonment, criminal fines, civil monetary penalties and exclusion from the participation in federal healthcare programs, such asMedicare and Medicaid.Federal Food Drug and Cosmetic ActThe Federal Food, Drug, and Cosmetic Act and its implementing regulations (FDCA) apply to drug product advertising and labeling. These lawsprohibit drug manufacturers and third parties acting on their behalf from marketing drug products for off-label uses. Violations of the FDCA can result incriminal and civil penalties, including imprisonment and civil monetary penalties. The U.S. Criminal Code may also apply and permit greater fines thanthose enumerated in the FDCA.Prescription Drug Marketing ActAs part of the sales and marketing process, pharmaceutical companies frequently provide healthcare providers with samples of approved drugs. ThePrescription Drug Marketing Act (PDMA) imposes requirements and limitations upon the distribution of drugs and drug samples, and prohibits states fromlicensing distributors of prescription drugs unless the state licensing program meets certain federal guidelines that include minimum standards for storage andhandling, as well as record keeping and other requirements. Violations of the PDMA may result in criminal and civil penalties. In addition, the PPACAimposes annual reporting requirements related to sample distribution.False Claims ActThe federal False Claims Act prohibits, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for paymentof government funds and knowingly making, or causing to be made or used, a false record or statement to get a false claim paid. Certain marketing practicesmay implicate the False Claims Act, including promotion of pharmaceutical products for unapproved uses, providing free product to customers with theexpectation that customers would bill federal programs for the product, or inflating prices reported to private price publication services used to set drugreimbursement rates under federal healthcare programs. In addition, PPACA amended the Social Security Act to provide that a claim including items orservices resulting from a violation of the Anti-Kickback Statute constitutes a false claim for purposes of the False Claims Act. Actions under the False ClaimsAct may be brought by the government or as a qui tam action by private individuals who may receive financial awards if their claims are successful. FalseClaims Act liability is potentially significant in the healthcare industry because the statute provides for treble damages and mandatory penalties of $5,500 to$11,000 per false claim or statement, which increased to a range of $11,181 to $22,363 in January 2018. Violations of the False Claims Act are alsopunishable by exclusion from participation in federal healthcare programs, such as Medicare and Medicaid. Pharmaceutical and other life sciences companiesoften resolve allegations without admissions of liability for significant and sometimes material amounts to avoid the uncertainty of treble damages and perclaim penalties that may be awarded in litigation. These companies may be required, however, to enter into corporate integrity agreements with thegovernment, which may impose substantial costs on companies to ensure compliance.Health Insurance Portability and Accountability Act and Health Information Technology for Economic and Clinical Health ActThe federal Health Insurance Portability and Accountability Act of 1996 (HIPAA), includes federal criminal statutory provisions that prohibit amongother actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-partypayors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcareoffense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement inconnection with the delivery of or payment for healthcare benefits, items or services.HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and their implementing regulations,impose certain requirements and restrictions on certain types of individuals and entities relating to the privacy and security of individually identifiablehealth information. Among other things, HITECH makes HIPAA’s security standards directly applicable not only to covered entities (e.g. health careproviders and health plans), but also to business associates, i.e., independent contractors or agents of covered entities that receive or obtain protected healthinformation in connection with providing a service for or on behalf of a covered entity. HITECH also created four new tiers of civil monetary penalties,amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civilactions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civilactions.28Table of ContentsPhysician Payment Sunshine ActThe federal Physician Payment Sunshine Act requires manufacturers of drugs, devices, biologics and medical supplies for which payment isavailable under Medicare, Medicaid or the Children’s Health Insurance Program to report annually (with certain exceptions) to CMS, information related topayments or other “transfers of value” made to physicians and teaching hospitals, and requires applicable manufacturers and group purchasing organizationsto report annually to CMS ownership and investment interests held by physicians and their immediate family members and payments or other ‘‘transfers ofvalue’’ to such physician owners. Failure to report relevant data may result in civil fines and/or penalties.Foreign Corrupt Practices ActThe U.S. Foreign Corrupt Practices Act (FCPA), prohibits U.S. corporations and their representatives and intermediaries from offering, promising,authorizing or making payments to any foreign government official, government staff member, political party or political candidate in an attempt to obtain orretain business abroad. The scope of the FCPA includes interactions with certain healthcare professionals in many countries. Other countries have enactedsimilar anti-corruption laws and/or regulations.Analogous State and Foreign LawsAnalogous state and foreign fraud and abuse laws and regulations, such as state anti-kickback and false claims laws, can apply to our businesspractices, including but not limited to research, distribution, sales or marketing arrangements and claims involving healthcare items or services reimbursed bynon-governmental third party payors and are generally broad and are enforced by many different federal and state agencies as well as through private actions.In addition to requiring reporting transfers of value, some states have imposed price reporting requirements, and an increasing number of countries worldwidehave either adopted or are considering similar laws requiring disclosure of various interactions with healthcare professionals. These state laws apply to itemsand services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor. In addition, a number of states requirepharmaceutical companies to report expenses relating to the marketing and promotion of pharmaceutical products and to report gifts and payments toindividual physicians in the states. Other states restrict when pharmaceutical companies may provide meals to prescribers or engage in other marketingrelated activities, or require pharmaceutical companies to implement compliance programs or marketing codes of conduct, and file periodic reports ordisclosures with states. Compliance with these laws requires significant resources and companies that do not comply may face civil penalties or otherconsequences.Outside the U.S., we are subject to similar regulations in those countries where we market and sell products, including with respect to transparency,bribery and other laws mentioned above. In some foreign countries, including major markets in the E.U. and Japan, the pricing of prescriptionpharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take nine to twelve months orlonger after the receipt of regulatory marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may be required toconduct a clinical trial that compares the cost-effectiveness of our product to other available therapies. Our business could be materially harmed ifreimbursement of our products is unavailable or limited in scope or amount or if pricing is set at unsatisfactory levels.The collection and processing of personal data in the E.U. is governed by the General Data Protection Regulation (GDPR), which became applicablein May 2018. The GDPR implements stringent operational requirements for processors and controllers of personal data, including expanded disclosuresabout how personal information is to be used, limitations on retention of information, requirements pertaining to health data and pseudonymised (i.e., key-coded) data, mandatory data breach notification requirements and standards for controllers to demonstrate that they have obtained valid consent for certaindata processing activities. The GDPR provides that members of the E.U. may make their own additional laws and regulations in relation to the processing ofgenetic, biometric or health data, which could result in differences between Member States, limit our ability to use and share personal data or could cause ourcosts to increase, and harm our business and financial condition. We are also subject to evolving and strict rules on the transfer of personal data out of theE.U. Failure to comply with E.U. data protection laws may result in fines and other administrative penalties, which may be onerous and adversely affect ourbusiness, financial condition, results of operations and prospects.Efforts to ensure that our business arrangements with third parties, and our business generally, will comply with applicable healthcare laws andregulations may involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with currentor future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operationsare found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal29Table of Contentsand administrative penalties, damages, fines, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and thecurtailment or restructuring of our operations.Additionally, drug prices are under significant scrutiny, and along with other health care costs, continue to be subject to intense political andsocietal pressures, which we anticipate will continue and escalate, including on a global basis. As a result, our business and reputation may be harmed, ourstock price may be adversely impacted and experience periods of volatility, and our results of operations may be adversely impacted.Other Laws and RegulationsThere are evolving legal requirements and other statutory and regulatory regimes that will continue to affect our business.Efforts to ensure that business activities and business arrangements comply with applicable healthcare laws and regulations can be costly formanufacturers of branded prescription products. If a manufacturer’s operations, including activities conducted by its sales or marketing teams, are found to bein violation of any of these laws or any other governmental regulations that apply to the company, the company may be subject to significant civil, criminaland administrative sanctions, including imprisonment, monetary penalties, damages, fines, exclusion from participation in federal healthcare programs, suchas Medicare and Medicaid, and the curtailment or restructuring of operations.We intend to seek regulatory approvals for our products in additional foreign jurisdictions, but we may not obtain any such approvals.We intend to market our products, alone or with others, in foreign jurisdictions. In order to market our products in foreign jurisdictions, we may berequired to obtain separate regulatory approvals and to comply with numerous and varying regulatory requirements. The approval procedure varies amongcountries and jurisdictions and can involve additional trials, and the time required to obtain approval may differ from that required to obtain FDA approval.Additionally, the foreign regulatory approval process may include all of the risks associated with obtaining FDA approval. For all of these reasons, we maynot obtain foreign regulatory approvals on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countriesor jurisdictions, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries orjurisdictions or by the FDA. We may not be able to file for regulatory approvals and may not receive necessary approvals to commercialize our products inany market. The failure to obtain these approvals could harm our business materially.We rely on a limited number of specialty pharmacies for distribution of HETLIOZ® in the U.S., and the loss of one or more of these specialtypharmacies or their failure to distribute HETLIOZ® effectively would materially harm our business.HETLIOZ® is only available for distribution through a limited number of specialty pharmacies in the U.S. A specialty pharmacy is a pharmacy thatspecializes in the dispensing of medications for complex or chronic conditions, which often require a high level of patient education and ongoingmanagement. The use of specialty pharmacies involves certain risks, including, but not limited to, risks that these specialty pharmacies will: •not provide us accurate or timely information regarding their inventories, the number of patients who are using HETLIOZ® or complaints aboutHETLIOZ®;•reduce their efforts or discontinue to sell or support or otherwise not effectively sell or support HETLIOZ®;•not devote the resources necessary to sell HETLIOZ® in the volumes and within the time frames that we expect;•be unable to satisfy financial obligations to us or others; or•cease operations.In addition, if one or more of our specialty pharmacies do not fulfill their contractual obligations to us, or refuse or fail to adequately serve patients,or their agreements are terminated without adequate notice, shipments of HETLIOZ®, and associated revenues, would be adversely affected. We expect that itwould take a significant amount of time if we were required to replace one or more of our specialty pharmacies.30Table of ContentsOur revenues from Fanapt® are substantially dependent on sales through a limited number of wholesalers, and such revenues may fluctuate fromquarter to quarter.We sell Fanapt® primarily through a limited number of pharmaceutical wholesalers in the U.S. The use of pharmaceutical wholesalers involvescertain risks, including, but not limited to, risks that these pharmaceutical wholesalers will: •not provide us accurate or timely information regarding their inventories, demand from wholesaler customers buying Fanapt® or complaintsabout Fanapt®;•reduce their efforts or discontinue to sell or support or otherwise not effectively sell or support Fanapt®;•not devote the resources necessary to sell Fanapt® in the volumes and within the time frames that we expect;•be unable to satisfy financial obligations to us or others; or•cease operations.Additionally, our reliance on a small number of wholesalers could cause revenues to fluctuate from quarter to quarter based on the buying patterns ofthese wholesalers. In addition, if any of these wholesalers fails to pay on a timely basis or at all, our business, financial condition and results of operationscould be materially adversely affected.We face substantial competition, which may result in others developing or commercializing products before or more successfully than we do.Our future success will depend on our ability to demonstrate and maintain a competitive advantage with respect to our products and our ability toidentify and develop additional products. Large, fully integrated pharmaceutical companies, either alone or together with collaborative partners, havesubstantially greater financial resources and have significantly greater experience than we do in: •developing products;•undertaking preclinical testing and clinical trials;•obtaining FDA and other regulatory approvals of products; and•manufacturing, marketing and selling products.These companies may invest heavily and quickly to discover and develop novel products that could make our products obsolete. Accordingly, ourcompetitors may succeed in obtaining patent protection, receiving FDA or foreign regulatory approval or commercializing superior products or othercompeting products before we do. Technological developments or the FDA or foreign regulatory approval of new therapeutic indications for existingproducts may make our products obsolete or may make them more difficult to market successfully, any of which could have a material adverse effect on ourbusiness, results of operations and financial condition.Our products, if successfully developed and approved for commercial sale, will compete with a number of drugs and therapies currentlymanufactured and marketed by major pharmaceutical and other biotechnology companies. Our products may also compete with new products currently underdevelopment by others or with products which may cost less than our products. Physicians, patients, third party payors and the medical community may notaccept or utilize any of our products that may be approved. If HETLIOZ®, Fanapt® and our other products, if and when approved, do not achieve significantmarket acceptance, our business, results of operations and financial condition would be materially adversely affected. We believe the primary competitors forHETLIOZ® and Fanapt® are as follows: •For HETLIOZ® in the treatment of Non-24, there are no FDA approved direct competitors. Sedative-Hypnotic treatments for certain sleep relateddisorders include, Ambien® (zolpidem) by Sanofi (including Ambien CR®), Lunesta® (eszopiclone) by Sunovion Pharmaceuticals Inc., Sonata®(zaleplon) by Pfizer Inc., Rozerem® (ramelteon) by Takeda Pharmaceuticals Company Limited, Silenor® (doxepin) by Pernix Therapeutics,Belsomra® (suvorexant) by Merck & Co., Inc., generic products such as zolpidem, trazodone and doxepin, and over-the-counter remedies suchas Benadryl® and Tylenol PM®. The class of melatonin agonists includes Rozerem® (ramelteon) by Takeda Pharmaceuticals Company Limited,Valdoxan® (agomelatine) by Servier, Circadin® (long-acting melatonin) by Neurim Pharmaceuticals Ltd. and the food supplement melatonin.Shift work and excessive sleepiness disorder treatments include Nuvigil® (armodafinil) and Provigil® (modafinil) both by Teva PharmaceuticalIndustries Ltd.31Table of Contents•For Fanapt® in the treatment of schizophrenia, the atypical antipsychotics competitors are Risperdal® (risperidone), including the long actinginjectable (LAI) formulation Risperdal Consta® and Invega® (paliperidone), including the LAI formulation Invega® Sustenna®, each by Ortho-McNeil-Janssen Pharmaceuticals, Inc., Zyprexa® (olanzapine), including the LAI formulation Zyprexa® RelprevvTM, each by Eli Lilly andCompany, Seroquel® and Seroquel XR® (quetiapine) by AstraZeneca PLC, Abilify® (aripiprazole) by Otsuka America Pharmaceutical Inc.,Abilify Maintena® (the LAI formulation of Abilify®) by Lundbeck/Otsuka America Pharmaceutical Inc., Geodon® (ziprasidone) by Pfizer Inc.,Saphris® (asenapine) by Allergan plc, Latuda® (lurasidone) by Sunovion Pharmaceuticals Inc., Rexulti® (brexpiprazole) by Lundbeck/OtsukaAmerica Pharmaceutical, Inc., AristadaTM (aripiprazole lauroxil) extended-release injectable suspension by Alkermes, Inc., VraylarTM(cariprazine) by Teva Pharmaceutical Industries Ltd., and generic clozapine, as well as the typical antipsychotics haloperidol, chlorpromazine,thioridazine, and sulpiride (all of which are generic).Additionally, we may face competition from newly developed generic products. Under the Hatch-Waxman Act newly approved drugs andindications may benefit from a statutory period of non-patent marketing exclusivity. The Hatch-Waxman Act seeks to stimulate competition by providingincentives to generic pharmaceutical manufacturers to introduce non-infringing forms of patented pharmaceutical products and to challenge patents onbranded pharmaceutical products. If we are unsuccessful at challenging an Abbreviated New Drug Application (ANDA), filed pursuant to the Hatch-WaxmanAct, cheaper generic versions of our products, which may be favored by insurers and third-party payors, may be launched commercially, which wouldsignificantly harm our business.FDA and foreign regulatory approval of our products is uncertain.The research, testing, manufacturing and marketing of products such as those that we have developed or that we are developing are subject toextensive regulation by federal, state and local government authorities, including the FDA, as well as foreign regulatory authorities in jurisdictions in whichwe seek approval. To obtain regulatory approval of such products, we must demonstrate to the satisfaction of the applicable regulatory agency that, amongother things, the product is safe and effective for its intended use. In addition, we must show that the manufacturing facilities used to produce such productsare in compliance with current Good Manufacturing Practices regulations (cGMP).The process of obtaining FDA and other required regulatory approvals and clearances can take many years and will require us to expend substantialtime and capital. Despite the time and expense expended, regulatory approval is never guaranteed. The number of preclinical and clinical trials that will berequired for FDA or foreign regulatory approval varies depending on the product, the disease or condition that the product is in development for, and therequirements applicable to that particular product. The FDA or applicable foreign regulatory agency can delay, limit or deny approval of a product for manyreasons, including that: •a product may not be shown to be safe or effective;•the FDA or foreign agency may interpret data from preclinical and clinical trials in different ways than we do;•the FDA or foreign agency may not approve our or our partners’ manufacturing processes or facilities;•a product may not be approved for all the indications we request;•the FDA or foreign agency may change its approval policies or adopt new regulations;•the FDA or foreign agency may not meet, or may extend, the Prescription Drug User Fee Act Amendments of 2017 (PDUFA-VI) date or itsforeign equivalent with respect to a particular NDA or foreign application; and•the FDA or foreign agency may not agree with our regulatory approval strategies or components of the regulatory filings, such as clinical trialdesigns.For example, if certain of our methods for analyzing trial data are not accepted by the FDA or the applicable foreign agency, we may fail to obtainregulatory approval for our products.Any delay or failure to obtain regulatory approvals for our products will result in increased costs, could diminish competitive advantages that wemay attain and would adversely affect the marketing and sale of our products. Other than HETLIOZ® in the U.S. and the 31 countries in Europe covered bythe centralized marketing authorization by the EC, and Fanapt® in the U.S., Mexico and Israel, we have not received, and may never receive, regulatoryapproval to market any of our products in any jurisdiction.32Table of ContentsEven following regulatory approval of our products, the FDA or the applicable foreign agency may impose limitations on the indicated uses forwhich such products may be marketed, subsequently withdraw approval or take other actions against us, or such products that are adverse to our business.The FDA and foreign agencies generally approve drugs for particular indications. An approval for a more limited indication reduces the size of the potentialmarket for the product. Product approvals, once granted, may be withdrawn or modified if problems occur after initial marketing.We and our partners also are subject to numerous federal, state, local and foreign laws, regulations and recommendations relating to safe workingconditions, laboratory and manufacturing practices, the environment and the use and disposal of hazardous substances used in connection with discovery,research and development work. In addition, we cannot predict the extent to which new governmental regulations might significantly impede the discovery,development, production and marketing of our products. We or our partners may be required to incur significant costs to comply with current or future laws orregulations, and we may be adversely affected by the cost of such compliance or the inability to comply with such laws or regulations.If our products are determined to be unsafe or ineffective in humans, whether commercially or in clinical trials, our business will be materiallyharmed.Despite the FDA’s approval of the NDA for HETLIOZ® in January 2014 and the NDA for Fanapt® in May 2009, the EC’s grant of the centralizedmarketing authorization for HETLIOZ® in July 2015, and the positive results of our completed trials for HETLIOZ® and Fanapt®, we are uncertain whethereither of these products will ultimately prove to be effective and safe in humans long term and in all uses. Frequently, products that have shown promisingresults in clinical trials have suffered significant setbacks in later clinical trials or even after they are approved for commercial sale. Future uses of ourproducts, whether in clinical trials or commercially, may reveal that the product is ineffective, unacceptably toxic, has other undesirable side effects, isdifficult to manufacture on a large scale, is uneconomical, infringes on proprietary rights of another party or is otherwise not fit for further use. If our productsare determined to be unsafe or ineffective in humans, our business will be materially harmed.Clinical trials for our products are expensive and their outcomes are uncertain. Any failure or delay in completing clinical trials for our productscould severely harm our business.Preclinical studies and clinical trials required to demonstrate the safety and efficacy of our products are time-consuming and expensive and togethertake several years to complete. Before obtaining regulatory approvals for the commercial sale of any of our products, we must demonstrate throughpreclinical testing and clinical trials that such product is safe and effective for use in humans. We have incurred, and we will continue to incur, substantialexpense for, and devote a significant amount of time to, preclinical testing and clinical trials.Historically, the results from preclinical testing and early clinical trials often have not predicted results of later clinical trials. A number of new drugshave shown promising results in clinical trials, but subsequently failed to establish sufficient safety and efficacy data to obtain necessary regulatoryapprovals. Clinical trials conducted by us or by third parties on our behalf may not demonstrate sufficient safety and efficacy to obtain the requisiteregulatory approvals for our products. Regulatory authorities may not permit us to undertake any additional clinical trials for our products, may force us tostop any ongoing clinical trials and it may be difficult to design efficacy studies for our products in new indications.Clinical development efforts performed by us may not be successfully completed, or completed in a timely manner. Completion of clinical trialsmay take several years or more. The length of time can vary substantially with the type, complexity, novelty and intended use of the products and the size ofthe prospective patient population. Our ability to enroll patients in, and the commencement and rate of completion of, clinical trials for our products may beaffected by many factors, including: •the size and nature of the patient population;•the design of the trial protocol for our clinical trials;•the eligibility and exclusion criteria for the trial in question;•the availability of competing therapies and competing clinical trials, and physician and patient perception of our product candidates and ourother product candidates being studied in relation to these other potential options;•the availability of raw materials and the possibility of raw materials expiring prior to their use;•difficulty in maintaining contact with patients after treatment, resulting in incomplete data;33Table of Contents•poor effectiveness of our products during clinical trials;•unforeseen safety issues or side effects;•the number and location of clinical sites in our clinical trials;•the proximity and availability of clinical trial sites for prospective patients;•the availability of time and resources at the institutions where clinical trials are and will be conducted;•the availability of adequate financing to fund ongoing clinical trial expenses;•the study endpoints that rely on subjective patient reported outcomes; and•governmental or regulatory delays and changes in regulatory requirements and guidelines.If we fail to complete successfully, or have difficulty enrolling a sufficient number of patients for, our clinical trials, we or they may not receive theregulatory approvals needed to market that product. Any such failure or difficulty could have a material adverse effect on our business.Our products may cause undesirable side effects or have other properties that could delay, prevent or result in the revocation of their regulatoryapproval or limit their marketability.Undesirable side effects caused by our products could interrupt, delay or halt clinical trials and could result in the denial of regulatory approval bythe FDA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing or continuing the commercializationof such products and generating revenues from their sale. We will continue to assess the side effect profile of our products in ongoing clinical developmentprograms. However, we cannot predict whether the commercial use of our approved products (or our products in development, if and when they are approvedfor commercial use) will produce undesirable or unintended side effects that have not been evident in the use of, or in clinical trials conducted for, suchproducts to date. Additionally, incidents of product misuse may occur. These events, among others, could result in product recalls, product liability actions orwithdrawals or additional regulatory controls, all of which could have a material adverse effect on our business, results of operations and financial condition.In addition, if after receiving marketing approval of a product, we or others identify undesirable side effects caused by such product, we could faceone or more of the following: •regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication;•regulatory authorities may withdraw their approval of the product;•we may be required to change the way the product is administered, conduct additional clinical trials or change the labeling of the product; and•our or the product’s reputation may suffer.Any of these events could prevent us from achieving or maintaining market acceptance of the affected product or could substantially increase thecosts and expenses of commercializing the product, which in turn could delay or prevent us from generating significant revenues from its sale.We have a history of operating losses, anticipate future losses and may never become profitable on a sustained basis.We have been engaged in identifying and developing products since March 2003, which has required, and will continue to require, significantresearch and development expenditures. The continued commercialization of HETLIOZ® and Fanapt® will require substantial additional expenditures.As of December 31, 2018, we had an accumulated deficit of $336.2 million and we cannot estimate with precision the extent of our future losses. Wemay not succeed in gaining additional market acceptance of HETLIOZ® and Fanapt® in the U.S. and we may not succeed in commercializing HETLIOZ® orFanapt® outside of the U.S. We may not be profitable even if our products are successfully commercialized. We may be unable to fully develop, obtainregulatory approval for, commercialize, manufacture, market, sell and derive revenue from our products in the timeframes we project, if at all, and ourinability to do so would materially and adversely impact the market price of our common stock and our ability to raise capital and continue operations.34Table of ContentsThere can be no assurance that we will achieve sustained profitability. Our ability to achieve sustained profitability in the future depends, in part,upon: •our ability to obtain and maintain regulatory approval for our products both in the U.S. and in foreign countries;•our level of success in commercializing HETLIOZ® in the U.S., Europe and other jurisdictions in which HETLIOZ® may receive regulatoryapproval, if any;•our level of success in raising awareness regarding Non-24 in the medical and patient communities;•our level of success in marketing and selling Fanapt® in the U.S. and our or our partners’ level of success in marketing and selling Fanapt® inIsrael and other jurisdictions in which we may receive regulatory approval, if any;•our ability to enter into and maintain agreements to develop and commercialize our products;•our ability to develop, have manufactured and market our products;•our ability to obtain adequate reimbursement coverage for our products from insurance companies, government programs and other third partypayors; and•our ability to obtain additional research and development funding from collaborative partners or funding for our products.In addition, the amount we spend will impact our profitability. Our spending will depend, in part, upon: •the costs of our marketing or awareness campaigns;•the progress of our research and development programs for our products, including clinical trials;•the time and expense that will be required to pursue FDA and/or foreign regulatory approvals for our products and whether such approvals areobtained on a timely basis, if at all;•the time and expense required to prosecute, enforce and/or challenge patent and other intellectual property rights;•the cost of third party manufacturers;•the number of additional products we pursue;•how competing technological and market developments affect our products;•the cost of possible acquisitions of technologies, products, product rights or companies;•the cost of obtaining licenses to use technology owned by others for proprietary products and otherwise;•the costs and effects of potential litigation; and•the costs associated with recruiting and compensating a highly skilled workforce in an environment where competition for such employees maybe intense.We may not achieve all or any of these goals and, thus, we cannot provide assurances that we will ever be profitable on a sustained basis or achievesignificant revenues. Even if we do achieve some or all of these goals, we may not achieve significant or sustained commercial success.Our ability to use net operating loss carryforwards and tax credit carryforwards to offset future taxable income may be limited as a result oftransactions involving our common stock.In general, under Section 382 of the Internal Revenue Code of 1986, as amended (IRC), a corporation that undergoes an “ownership change” issubject to limitations on its ability to utilize its pre-change net operating losses (NOLs) and certain other tax assets (tax attributes) to offset future taxableincome. In general, an ownership change occurs if the aggregate stock ownership of certain stockholders increases by more than 50 percentage points oversuch stockholders’ lowest percentage ownership during the testing period (generally three years). Transactions involving our common stock, even thoseoutside our control, such as purchases or sales by investors, within the testing period could result in an ownership change. A limitation on our ability toutilize some or all of our NOLs or credits could have a material adverse effect on our results of operations and cash flows. Ownership changes occurred in theyears ending December 31, 2014 and 2008. We believe that the ownership changes in 2014 and 2008 will not impact our ability to utilize NOL and creditcarryforwards; however, future ownership changes may cause our existing tax attributes to have additional limitations.35Table of ContentsIf we fail to obtain the capital necessary to fund our research and development activities and commercialization efforts, we may be unable to continueoperations or we may be forced to share our rights to commercialize our products with third parties on terms that may not be attractive to us.Our activities will necessitate significant uses of working capital throughout 2019 and beyond. It is uncertain whether our existing funds will besufficient to meet our operating needs. As of December 31, 2018, our total cash and cash equivalents and marketable securities were $257.4 million. Our longterm capital requirements are expected to depend on many factors, including, among others: •our level of success in commercializing HETLIOZ® and Fanapt® globally;•outcomes of ongoing and potential patent litigation;•costs of developing and maintaining sales, marketing and distribution channels and our ability to sell our products;•market acceptance of our products;•costs involved in establishing and maintaining manufacturing capabilities for commercial quantities of our products;•the number of potential formulations and products in development;•progress with preclinical studies and clinical trials;•time and costs involved in obtaining regulatory (including FDA) approval;•costs involved in preparing, filing, prosecuting, maintaining and enforcing patent, trademark and other intellectual property claims;•competing technological and market developments;•costs for recruiting and retaining employees and consultants;•costs for training physicians; and•legal, accounting, insurance and other professional and business related costs.As a result, we may need to raise additional capital to fund our anticipated operating expenses and execute on our business plans. In our capital-raising efforts, we may seek to sell debt securities or additional equity securities, obtain a bank credit facility, or enter into partnerships or other collaborationagreements. The sale of additional equity or debt securities, if convertible, could result in dilution to our stockholders and may also result in a lower price forour common stock. The incurrence of indebtedness would result in increased fixed obligations and could also result in covenants that could restrict ouroperations. However, we may not be able to raise additional funds on acceptable terms, or at all. If we are unable to secure sufficient capital to fund ourplanned activities, we may not be able to continue operations, or we may have to enter into partnerships or other collaboration agreements that could requireus to share commercial rights to our products to a greater extent or at earlier stages in the drug development process than is currently intended. Thesepartnerships or collaborations, if consummated prior to proof-of-efficacy or safety of a given product, could impair our ability to realize value from thatproduct. If additional financing is not available when required or is not available on acceptable terms, we may be unable to fund our operations and plannedgrowth, develop or enhance our technologies or products, take advantage of business opportunities or respond to competitive market pressures, any of whichwould materially harm our business, financial condition and results of operations.If our contract research organizations (CROs) do not successfully carry out their duties or if we lose our relationships with contract researchorganizations, our drug development efforts could be delayed.Our arrangements with CROs are critical to our success in bringing our products to the market and promoting such marketed products profitably. Weare dependent on CROs, third-party vendors and investigators for preclinical testing and clinical trials related to our drug discovery and development effortsand we will likely continue to depend on them to assist in our future discovery and development efforts. These parties are not our employees and we cannotcontrol the amount or timing of resources that they devote to our programs. As such, they may not complete activities on schedule or may not conduct ourclinical trials in accordance with regulatory requirements or our stated protocols. The parties with which we contract for execution of our clinical trials play asignificant role in the conduct of the trials and the subsequent collection and analysis of data. If they fail to devote sufficient time and resources to our drugdevelopment programs or if their performance is substandard, it will delay the development, approval and commercialization of our products. Moreover,these parties may also36Table of Contentshave relationships with other commercial entities, some of which may compete with us. If they assist our competitors, it could harm our competitive position.Our CROs could merge with or be acquired by other companies or experience financial or other setbacks unrelated to our collaboration that could,nevertheless, materially adversely affect our business, results of operations and financial condition.If we lose our relationship with any one or more of these parties, we could experience a significant delay in both identifying another comparableprovider and then contracting for its services. We may be unable to retain an alternative provider on reasonable terms, if at all. Even if we locate analternative provider, it is likely that this provider may need additional time to respond to our needs and may not provide the same type or level of service asthe original provider. In addition, any provider that we retain will be subject to current Good Laboratory Practices, and similar foreign standards and we donot have control over compliance with these regulations by these providers. Consequently, if these practices and standards are not adhered to by theseproviders, the development and commercialization of our products could be delayed.We rely on a limited number of third party manufacturers to formulate and manufacture our products and our business will be seriously harmed ifthese manufacturers are not able to satisfy our demand and alternative sources are not available.Our expertise is primarily in the research and development and preclinical and clinical trial phases of product development. We do not have an in-house manufacturing capability and depend completely on a small number of third-party manufacturers and active pharmaceutical ingredient formulators forthe manufacture of our products. Therefore, we are dependent on third parties for our formulation development and manufacturing of our products. This mayexpose us to the risk of not being able to directly oversee the production and quality of the manufacturing process and provide ample commercial supplies tosuccessfully launch and maintain the marketing of our products. Furthermore, these third party contractors, whether foreign or domestic, may experienceregulatory compliance difficulty, mechanical shut downs, employee strikes, or other unforeseeable events that may delay or limit production. Our inability toadequately establish, supervise and conduct (either ourselves or through third parties) all aspects of the formulation and manufacturing processes would havea material adverse effect on our ability to develop and commercialize our products.We have agreements in place with Patheon Pharmaceuticals Inc. and Patheon Inc. (collectively, Patheon), subsidiaries of Thermo Fisher Scientific,for the manufacture of HETLIOZ® and Fanapt®.In January 2014, we entered into a manufacturing agreement with Patheon for the manufacture of commercial supplies of HETLIOZ® 20 mg capsulesat Patheon’s Cincinnati, Ohio manufacturing site. In May 2016, we entered into a manufacturing agreement with Patheon for the manufacture of commercialsupplies of Fanapt® tablets at Patheon’s Mississauga, Ontario, Canada manufacturing site. We do not have exclusive long-term agreements with any otherthird party manufacturers of our products. If our current manufacturers, or any other third party manufacturer, is unable or unwilling to perform its obligationsunder our manufacturing agreements for any reason, we may not be able to locate alternative acceptable manufacturers or formulators or enter into favorableagreements with them. Any inability to acquire sufficient quantities of our products in a timely manner from these third parties could adversely affect sales ofour products, delay clinical trials and prevent us from developing our products in a cost-effective manner or on a timely basis. In addition, manufacturers ofour products are subject to cGMP and similar foreign standards and we do not have control over compliance with these regulations by our manufacturers. Ifone of our contract manufacturers fails to maintain compliance, the production of our products could be interrupted, resulting in delays and additional costs.In addition, if the facilities of such manufacturers do not pass a pre-approval or post-approval plant inspection, the FDA will not grant approval and mayinstitute restrictions on the marketing or sale of our products.Our manufacturing strategy presents the following additional risks: •because most of our third-party manufacturers and formulators are located outside of the U.S., there may be difficulties in importing our productsor their components into the U.S. as a result of, among other things, FDA import inspections, incomplete or inaccurate import documentation ordefective packaging; and•because of the complex nature of our products, our manufacturers may not be able to successfully manufacture our products in a cost-effectiveand/or timely manner.37Table of ContentsMaterials necessary to manufacture our products may not be available on commercially reasonable terms, or at all, which may delay the development,regulatory approval and commercialization of our products.We rely on manufacturers to purchase from third-party suppliers the materials necessary to produce our products for clinical trials andcommercialization. Suppliers may not sell these materials to such manufacturers at the times we need them or on commercially reasonable terms. We do nothave any control over the process or timing of the acquisition of these materials by these manufacturers. Moreover, we currently do not have any agreementsfor the commercial production of these materials. If the manufacturers are unable to obtain these materials for our clinical trials, product testing, potentialregulatory approval of our products and commercial scale manufacturing could be delayed, significantly affecting our ability to further develop andcommercialize our products. If we, our manufacturers are unable to purchase these materials for our products, there would be a shortage in supply or thecommercial launch of such products would be delayed, which would materially and adversely affect our ability to generate revenues from the sale of suchproducts.If we cannot identify, or enter into licensing arrangements for, new products, our ability to develop a diverse product portfolio will be limited.A component of our business strategy is acquiring rights to develop and commercialize products discovered or developed by other pharmaceuticaland biotechnology companies for which we may find effective uses and markets through our unique pharmacogenetics and pharmacogenomics expertise forthe treatment of central nervous system disorders. Competition for the acquisition of these products is intense. If we are not able to identify opportunities toacquire rights to commercialize additional products, we may not be able to develop a diverse portfolio of products and our business may be harmed.Additionally, it may take substantial human and financial resources to secure commercial rights to promising products. Moreover, if other firms developpharmacogenetics and pharmacogenomics capabilities, we may face increased competition in identifying and acquiring additional products.If we lose key scientists or management personnel, or if we fail to recruit additional highly skilled personnel, it will impair our ability to identify,develop and commercialize products.We are highly dependent on principal members of our management team and scientific staff, including our Chief Executive Officer, Mihael H.Polymeropoulos, M.D. These executives each have significant pharmaceutical industry experience. The loss of any such executives, includingDr. Polymeropoulos, or any other principal member of our management team or scientific staff, would impair our ability to identify, develop and market newproducts. Our management and other employees may voluntarily terminate their employment with us at any time. The loss of the services of these or otherkey personnel, or the inability to attract and retain additional qualified personnel, could result in delays to development or approval, loss of sales anddiversion of management resources. In addition, we depend on our ability to attract and retain other highly skilled personnel, including research scientists.Competition for qualified personnel is intense, and the process of hiring and integrating such qualified personnel is often lengthy. We may be unable torecruit such personnel on a timely basis, if at all, which would negatively impact our development and commercialization programs.Additionally, we do not currently maintain “key person” life insurance on the lives of our executives or any of our employees. This lack of insurancemeans that we may not have adequate compensation for the loss of the services of these individuals.Product liability lawsuits could divert our resources, result in substantial liabilities and reduce the commercial potential of our products.The risk that we may be sued on product liability claims is inherent in the development and sale of pharmaceutical products. For example, we face arisk of product liability exposure related to the testing of our products in clinical trials and will face even greater risks upon commercialization of ourproducts. We believe that we may be at a greater risk of product liability claims relative to other pharmaceutical companies because certain of our productsare intended to treat central nervous system disorders, among others, and it is possible that we may be held liable for the behavior and actions of patients whouse our products. These lawsuits may divert our management from pursuing our business strategy and may be costly to defend. In addition, if we are heldliable in any of these lawsuits, we may incur substantial liabilities and we may be forced to limit or forego further commercialization of one or more of ourproducts. Although we maintain product liability insurance, our aggregate coverage limit under this insurance is $30.0 million, and while we believe thisamount of insurance is sufficient to cover our product liability exposure, these limits may not be high enough to fully cover potential liabilities. As ourdevelopment activities and commercialization efforts progress and we sell our products, this coverage may be inadequate, we may be unable to obtainadequate coverage at an acceptable cost or we may be unable to get adequate coverage at all or our insurer may disclaim coverage as to a future claim. Thiscould prevent the commercialization or limit the commercial potential38Table of Contentsof our products. Even if we are able to maintain insurance that we believe is adequate, our results of operations and financial condition may be materiallyadversely affected by a product liability claim. Uncertainties resulting from the initiation and continuation of products liability litigation or otherproceedings could have a material adverse effect on our ability to compete in the marketplace. Product liability litigation and other related proceedings mayalso require significant management time.E.U. Member States tend to impose strict price controls, which may delay or prevent the further commercial launch or impede the commercial successof HETLIOZ® in Europe and adversely affect our future results of operations.In the E.U., prescription drug pricing and reimbursement are subject to governmental control and reimbursement mechanisms used by private andpublic health insurers in the E.U. vary by Member State. For the public systems, reimbursement is determined by guidelines established by the legislature orresponsible national authority. As elsewhere, inclusion in reimbursement catalogues focuses on the medical usefulness, need, quality and economic benefitsto patients and the health care system. Acceptance for reimbursement comes with cost, use and often volume restrictions, which can vary by Member State.Although we have received marketing authorization for HETLIOZ® from the EC, pricing negotiations with governmental authorities may take a considerableamount of time in those Member States that impose price controls. For example, we launched HETLIOZ® commercially in Germany in August 2016, andconcluded our pricing negotiations with German authorities in October 2017. In addition, to obtain reimbursement or pricing approval for HETLIOZ® insome Member States, we may be required to conduct a clinical trial that compares the cost-effectiveness of HETLIOZ®, to other available therapies.Some Member States require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins aftermarketing or product licensing approval is granted. In some Member States, prescription pharmaceutical pricing remains subject to continuing governmentalcontrol even after initial approval is granted. As a result, we may be subject to lengthy price regulations that delay or prevent the commercial launch ofHETLIOZ® in a particular Member State and negatively impact the revenues that are generated from the sale of HETLIOZ® in that country. If reimbursementof HETLIOZ® is unavailable or limited in scope or amount, or if pricing for HETLIOZ® is set at unsatisfactory levels or takes too long to establish, or if thereis competition from lower priced cross-border sales, our results of operations will be negatively affected.We may not be able to effectively market and sell our future products, if approved, in the U.S.We plan to continue to build our sales and marketing capabilities in the U.S. to commercialize future products, if approved. Our current sales andmarketing capabilities in the U.S. may not be adequate to support the commercialization of future products and we would expect to build such capabilities byinvesting significant amounts of financial and management resources. Furthermore, the cost of establishing and maintaining marketing and sales capabilitiesmay not be justifiable in light of the revenues generated by any future products.If we are unable to establish and maintain adequate sales and marketing capabilities for future products or are unable to do so in a timely manner, wemay not be able to generate product revenues from these products which may prevent us from reaching or maintaining profitability.Legislative or regulatory reform of the healthcare system in the U.S. may affect our ability to sell our products profitably.PPACA substantially changes the way healthcare is financed by both governmental and private insurers, and significantly impacts thepharmaceutical industry. PPACA contains a number of provisions that are expected to impact our business and operations, in some cases in ways we cannotcurrently predict. Changes that may affect our business if we commercialize our products in the future include those governing enrollment in federalhealthcare programs, reimbursement changes, rules regarding prescription drug benefits under the health insurance exchanges, and fraud and abuse andenforcement. In addition, continued implementation of PPACA may result in the expansion of new programs such as Medicare payment for performanceinitiatives, and may impact existing government healthcare programs, such as by improving the physician quality reporting system and feedback program.Additional provisions of PPACA may negatively affect our revenues from products that we commercialize in the future. For example, as part ofPPACA’s provisions closing a coverage gap that currently exists in the Medicare Part D prescription drug program, manufacturers of branded prescriptiondrugs are required to provide a 50% discount on branded prescription drugs dispensed to beneficiaries within this coverage gap. Public Law No. 115-123,also known as the Bipartisan Budget Act of 2018 enacted on February 9, 2018 increased the manufacturer discount from 50% to 70% effective in 2019 forapplicable drugs. Medicare Part D is a prescription drug benefit available to all Medicare beneficiaries. It is a voluntary benefit39Table of Contentsthat is implemented through private plans under contractual arrangements with the federal government. Similar to pharmaceutical coverage through privatehealth insurance, Part D plans negotiate discounts from drug manufacturers and pass on some of those savings to Medicare beneficiaries. PPACA also makeschanges to the Medicaid Drug Rebate Program, discussed in more detail below, including increasing the minimum rebate from 15.1% to 23.1% of the averagemanufacturer price for most innovator products. On February 1, 2016, CMS, the federal agency that administers the Medicare and Medicaid programs, issuedfinal regulations to implement the changes to the Medicaid Drug Rebate Program under PPACA. These regulations became effective on April 1, 2016.Many of PPACA’s most significant reforms did not take effect until 2014 or thereafter, and the resulting new programs and requirements willcontinue to evolve in the next few years. Some states have chosen not to expand their Medicaid programs by raising the income limit to 133% of the federalpoverty level. In part because not all states have expanded their Medicaid programs, it is unclear whether there will be more uninsured patients thananticipated when Congress passed PPACA. For each state that has opted not to expand its Medicaid program, there will be fewer insured patients overall. Anincrease in the proportion of uninsured patients who are prescribed products resulting from our proprietary or partnered programs could impact the futuresales of any products that are commercialized in the future and our business and results of operations.Further, in September 2007, the Food and Drug Administration Amendments Act of 2007 was enacted giving the FDA enhanced post-marketingauthority including the authority to require post-marketing studies and clinical trials, labeling changes based on new safety information and compliance withRisk Evaluation and Mitigation Strategy (REMS) approved by the FDA. The FDA’s exercise of this authority could result in delays or increased costs duringproduct development, clinical trials and regulatory review, increased costs to ensure compliance with post-approval regulatory requirements and potentialrestrictions on the sale and/or distribution of approved products.In addition, other legislative changes have been proposed and adopted in the U.S. since PPACA was enacted. On August 2, 2011, the BudgetControl Act of 2011 among other things, created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked withrecommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering thelegislation’s automatic reduction to several government programs. This includes aggregate reductions to Medicare payments to providers of up to 2% perfiscal year, starting in 2013, which will remain in effect until 2024 unless additional congressional action is taken. On January 2, 2013, the AmericanTaxpayer Relief Act of 2012 was signed into law, which, among other things, increased the statute of limitations period for the government to recoveroverpayments to providers from three to five years. We expect that additional federal healthcare reform measures will be adopted in the future, any of whichcould limit the amounts that federal and state governments will pay for healthcare products and services, and in turn could significantly reduce the projectedvalue of certain development projects and reduce our profitability.More recently, the current presidential administration and many members of the U.S. Congress have attempted to repeal and replace PPACA, butthey have been unsuccessful in doing so as of the date of the filing of this report. We cannot predict the ultimate form or timing of any repeal or replacementof PPACA or the effect such repeal or replacement would have on our business. Regardless of the impact of repeal or replacement of PPACA on us, thegovernment has shown significant interest in pursuing healthcare reform and reducing healthcare costs.We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts thatfederal and state governments will pay for healthcare products and services, which could result in reduced demand for our products once approved oradditional pricing pressures, and may adversely affect our operating results.Significant developments arising from changes in the political climate could have a material adverse effect on us.Changes in U.S. social, political, regulatory and economic conditions or in laws and policies governing foreign trade, manufacturing, developmentand investment, and any negative sentiments towards the U.S. as a result of such changes, could adversely affect our business.Additionally, in June 2016, the United Kingdom (U.K.) held a referendum and voted in favor of leaving the E.U. In February 2017, the U.K.parliament voted to allow the U.K. to exit the E.U. by passing a bill that gives the prime minister of the U.K. the authority to invoke Article 50 of the LisbonTreaty. The prime minister of the U.K. has negotiated with the E.U. to provide an orderly transition as the U.K. exits the E.U., but has been unsuccessful inhaving the U.K. assembly approve the agreement, which has created additional uncertainty. This referendum has created political and economic uncertainty,particularly in the U.K. and the E.U., and this uncertainty may last for years. There are many ways in which our business could be affected, only some ofwhich we can identify.40Table of ContentsThe referendum, and the likely withdrawal of the U.K. from the E.U. it triggers, has caused and, along with events that could occur in the future as aconsequence of the U.K.’s withdrawal, including the possible breakup of the U.K., may continue to cause significant volatility in global financial markets,including in global currency and debt markets. This volatility could cause a slowdown in economic activity in the U.K., Europe or globally, which couldadversely affect our operating results and growth prospects. In addition, our business could be negatively affected by new trade agreements between the U.K.and other countries, including the U.S., and by the possible imposition of trade or other regulatory barriers in the U.K., especially if the U.K. withdraws fromthe E.U. These possible negative impacts, and others resulting from the U.K.’s actual or threatened withdrawal from the E.U., may adversely affect ouroperating results and growth prospects as well as the manner in which we conduct our business operations in Europe.U.S. federal income tax reform could adversely affect us.In December 2017, U.S. federal tax legislation, commonly referred to as the Tax Cuts and Jobs Act (TCJA), was signed into law, significantlyreforming the Internal Revenue Code of 1986, as amended (IRC). The TCJA, among other things, includes changes to U.S. federal tax rates, imposessignificant additional limitations on the deductibility of interest, allows for the expensing of capital expenditures, puts into effect the migration from a“worldwide” system of taxation to a territorial system and modifies or repeals many business deductions and credits.We completed our accounting analysis of the impact of the TCJA in the fourth quarter of 2018. However, we continue to examine the impact theTCJA may have on our business. The TCJA is a far-reaching and complex revision to the U.S. federal income tax laws with disparate and, in some cases,countervailing impacts on different categories of taxpayers and industries. The long-term impact of the TCJA on the overall economy, the industries in whichwe operate and our business cannot be reliably predicted at this early stage of the new law’s implementation. There can be no assurance that the TCJA willnot negatively impact our operating results, financial condition, and future business operations. The impact of the TCJA is based on our management’scurrent knowledge and assumptions, following consultation with our tax advisors. Because of our valuation allowance in the U.S., ongoing tax effects of theTCJA are not expected to materially change our effective tax rate in future periods. The impact of the TCJA on holders of common stock is uncertain andcould be materially adverse. This Annual Report does not discuss any such tax legislation or the manner in which it might affect investors in common stock.Investors should consult with their own tax advisors with respect to such legislation and the potential tax consequences of investing in common stock.New legislation or regulation which could affect our tax burden could be enacted by any governmental authority. We cannot predict the timing orextent of such tax-related developments which could have a negative impact on our financial results. Additionally, we use our best judgment in attempting toquantify and reserve for these tax obligations. However, a challenge by a taxing authority, our ability to utilize tax benefits such as carryforwards or taxcredits, or a deviation from other tax-related assumptions may cause actual financial results to deviate from previous estimates.Future transactions may harm our business or the market price of our stock.We regularly review potential transactions related to technologies, products or product rights and businesses complementary to our business. Thesetransactions could include: •mergers;•acquisitions;•strategic alliances;•licensing agreements; and•co-promotion and similar agreements.We may choose to enter into one or more of these transactions at any time, which may cause substantial fluctuations in the market price of our stock.Moreover, depending upon the nature of any transaction, we may experience a charge to earnings, which could also materially adversely affect our results ofoperations and could harm the market price of our stock.We may undertake strategic acquisitions in the future, and difficulties integrating such acquisitions could damage our ability to achieve or sustainprofitability.Although we have no experience in acquiring businesses, we may acquire businesses or assets that complement or augment our existing business. Ifwe acquire businesses with promising products or technologies, we may not be able to realize41Table of Contentsthe benefit of acquiring such businesses if we are unable to move one or more products through preclinical and/or clinical development to regulatoryapproval and commercialization. Integrating any newly acquired businesses or technologies could be expensive and time-consuming, resulting in thediversion of resources from our current business. We may not be able to integrate any acquired business successfully. We cannot assure you that, following anacquisition, we will achieve revenues, specific net income or loss levels that justify the acquisition or that the acquisition will result in increased earnings, orreduced losses, for the combined company in any future period. Moreover, we may need to raise additional funds through public or private debt or equityfinancing to acquire any businesses, which would result in dilution for stockholders or the incurrence of indebtedness and may not be available on termswhich would otherwise be acceptable to us. We may not be able to operate acquired businesses profitably or otherwise implement our growth strategysuccessfully.Our operating results may fluctuate significantly due to a number of factors which make our future results difficult to predict and could cause ouroperating results to fall below expectations or our guidance.Our operating results will continue to be subject to fluctuations. The revenues we generate and our operating results will be affected by numerousfactors, including: •product sales;•cost of product sales;•marketing and other expenses;•manufacturing or supply issues;•the timing and amount of royalties or milestone payments;•our addition or termination of development programs;•variations in the level of expenses related to our products or future development programs;•regulatory developments affecting our products or those of our competitors;•our execution of collaborative, licensing or other arrangements, and the timing of payments we may make or receive under these arrangements;•any intellectual property infringement or other lawsuit in which we may become involved; and•the timing and recognition of stock-based compensation expense.If our operating results fall below the expectations of investors or securities analysts or below any guidance we may provide, the price of ourcommon stock could decline substantially. Furthermore, any fluctuations in our operating results may, in turn, cause the price of our stock to fluctuatesubstantially. We believe that comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our futureperformance.We are increasingly dependent on information technology systems, infrastructure and data. Cybersecurity breaches could expose us to liability,damage our reputation, compromise our confidential information or otherwise adversely affect our business.We are increasingly dependent upon information technology systems, infrastructure and data. Our computer systems may be vulnerable to serviceinterruption or destruction, malicious intrusion and random attack. Security breaches pose a risk that sensitive data, including intellectual property, tradesecrets or personal information may be exposed to unauthorized persons or to the public. Cyber-attacks are increasing in their frequency, sophistication andintensity, and have become increasingly difficult to detect. Cyber-attacks could include the deployment of harmful malware, denial-of service, socialengineering and other means to affect service reliability and threaten data confidentiality, integrity and availability. Our key business partners face similarrisks, and a security breach of their systems could adversely affect our security posture. While we continue to invest in data protection and informationtechnology, there can be no assurance that our efforts will prevent service interruptions, or identify breaches in our systems, that could adversely affect ourbusiness and operations and/or result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm.Our internal computer systems, or those of our collaborator, CROs or other contractors or consultants, may fail or suffer security breaches, whichcould result in a material disruption of development programs for our product candidates.Despite the implementation of security measures, our internal computer systems and those of our collaborators, CROs, and other contractors andconsultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters,42Table of Contentsterrorism, war and telecommunication and electrical failures. Information security risks have significantly increased in recent years in part due to theproliferation of new technologies and the increased sophistication and activities of organized crime, hackers, terrorists and other external parties, includingforeign state actors. As cyber threats continue to evolve, we may be required to expend significant additional resources to continue to modify or enhance ourprotective measures or to investigate and remediate any information security breaches.While we have not experienced any such system failure, accident or security breach to date, if such an event were to occur and cause interruptions inour operations, it could result in a material disruption of our independent drug development programs. For example, the loss of clinical trial data fromongoing or future clinical trials for any of our product candidates could result in delays in regulatory approval efforts and significantly increase costs torecover or reproduce the data. Our information security systems are also subject to laws and regulations requiring that we take measures to protect the privacyand security of certain information we gather and use in our business. For example, HIPAA and its implementing regulations impose, among otherrequirements, certain regulatory and contractual requirements regarding the privacy and security of personal health information. In addition to HIPAA,numerous other federal and state laws, including, without limitation, state security breach notification laws, state health information privacy laws and federaland state consumer protection laws, govern the collection, use, disclosure and storage of personal information. To the extent that any disruption or securitybreach were to result in a loss of or damage to data or applications, or inappropriate disclosure of confidential or proprietary information or personal healthinformation, we could incur substantial liability, our reputation would be damaged, and the further development of our product candidates could be delayed.Risks related to intellectual property and other legal mattersOur rights to develop and commercialize our products are subject in part to the terms and conditions of licenses or sublicenses granted to us by otherpharmaceutical companies.Our rights to our product portfolio are based in part on patents and other intellectual property licensed from third-parties. These third parties maygenerally terminate the license agreements under certain circumstances, including a material breach of the agreement by the other. In the event we terminateour license, or if the third-party terminates our license due to our breach, rights to the intellectual property revert back to the licensor. Any termination orreversion of our rights to develop or commercialize our products would have a material adverse effect on our business.If our efforts to protect the proprietary nature of the intellectual property related to our products are not adequate, we may not be able to competeeffectively in our markets.Method of treatment patents protect the use of a product for the method specified in the patent claims. This type of patent does not prevent acompetitor from making and marketing a product that is identical to our product for a use that is outside the scope of the patented method. Moreover, even ifcompetitors do not actively promote their product for our patented methods, physicians may prescribe these products “off-label.” Although off-labelprescriptions may infringe or contribute to the infringement of method of treatment patents, such infringement may be difficult to prevent.Our patents and patent applications may be challenged or fail to result in issued patents and our existing or future patents may be too narrow toprevent third parties from developing or designing around these patents. In addition, we generally rely on trade secret protection and confidentialityagreements to protect certain proprietary know-how that is not patentable, for processes for which patents are difficult to enforce and for any other elements ofour drug development processes that involve proprietary know-how, information and technology that is not covered by patent applications. While we requireall of our employees, consultants, advisors and any third parties who have access to our proprietary know-how, information and technology to enter intoconfidentiality agreements, we cannot be certain that this know-how, information and technology will not be disclosed or that competitors will not otherwisegain access to our trade secrets or independently develop substantially equivalent information and techniques. Further, the laws of some foreign countries donot protect proprietary rights to the same extent as the laws of the U.S. As a result, we may encounter significant problems in protecting and defending ourintellectual property both in the U.S. and abroad. If we are unable to protect or defend the intellectual property related to our technologies, we will not beable to establish or maintain a competitive advantage in our market.Even if our patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, preventcompetitors from competing with us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our owned orlicensed patents by developing similar or alternative technologies or products in a non-infringing manner. Our competitors may seek to market genericversions of any approved products by submitting ANDAs to the FDA in which they claim that patents owned or licensed by us are invalid, unenforceableand/or not infringed. Alternatively, our competitors may seek approval to market their own products similar to or otherwise competitive with our products. Inthese circumstances, we may need to defend and/or assert our patents, including by filing lawsuits43Table of Contentsalleging patent infringement. In any of these types of proceedings, a court or other agency with jurisdiction may find our patents invalid and/orunenforceable. Even if we have valid and enforceable patents, these patents still may not provide protection against competing products or processessufficient to achieve our business objectives.The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may bechallenged in the courts or patent offices in the U.S. and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claimsbeing narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar oridentical technology and products, or limit the duration of the patent protection of our technology and products. In addition, given the amount of timerequired for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly aftersuch candidates are commercialized.We are, have been, and may continue to be, involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming andunsuccessful, and third parties may challenge the validity or enforceability of our patents and they may be successful.Even where laws provide protection or we are able to obtain patents, costly and time-consuming litigation may be necessary to enforce anddetermine the scope of our proprietary rights, and the outcome of such litigation would be uncertain. Moreover, any actions we may bring to enforce ourintellectual property against our competitors could provoke them to bring counterclaims against us, and some of our competitors have substantially greaterintellectual property portfolios than we have. To counter infringement or unauthorized use of any patents we may obtain, we may be required to fileinfringement claims, which can be expensive and time-consuming to litigate. In addition, if we or one of our future collaborators were to initiate legalproceedings against a third party to enforce a patent covering one of our products, current product candidates, or one of our future products, the defendantcould counterclaim that the patent is invalid or unenforceable. In patent litigation in the U.S., defendant counterclaims alleging invalidity orunenforceability are commonplace and challenges to validity of patents in certain foreign jurisdictions are common as well. Grounds for a validity challengecould be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, non-enablement or lack of statutory subjectmatter. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant materialinformation from the U.S. Patent and Trademark Office, or made a materially misleading statement, during prosecution. We may assert the patents in Hatch-Waxman litigation against the party filing the ANDA to keep the competing product off of the market until the patents expire but there is a risk that we willnot succeed. The party filing the ANDA may also counterclaim in the litigation that our patents are not valid or unenforceable, and the court may find one ormore claims of our patents invalid or unenforceable. If this occurs, a competing generic product could be marketed prior to expiration of our patents listed inthe FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the “Orange Book,” which would harm our business.We have been and continue to be involved in number of lawsuits with a variety of generic drug manufacturers who have filed ANDAs relating tocertain of our patents. We have been successful in asserting that these third parties have infringed certain of our patents, but we may not be successful in suchlawsuits in the future. Please see Part I, Item 3, Legal Proceedings, of this annual report on Form 10-K for additional information.If we do not obtain protection under the Hatch-Waxman Act and similar foreign legislation to extend our patents and to obtain market exclusivity forour products, our business will be harmed.The Hatch-Waxman Act provides for an extension of patent term for drugs for a period of up to five years to compensate for time spent indevelopment. The HETLIOZ® U.S. new chemical entity (NCE) patent (the primary patent covering the product as a new composition of matter) received thefull five-year patent term extension under the Hatch-Waxman Act and so, assuming that we continue to have rights under our license agreement with respectto this product, this patent in the U.S. expires in December 2022. We also own HETLIOZ® U.S. method of treatment patents (directed to the approved methodof treatment as described in the HETLIOZ® label approved by the FDA), which expire normally in 2033 and 2034, and a drug substance patent which expiresin 2035. The Fanapt® U.S. NCE patent received the full five-year patent term extension under the Hatch-Waxman Act and so this patent in the U.S. expired inNovember 2016. In November 2013, a patent directed to a method of treating patients with Fanapt® based on genotype was issued to us by the U.S. Patentand Trademark Office. This patent, which was listed in the Orange Book in January 2015, is set to expire in 2027. Please see the risk factor entitled “We havebeen, and may be, involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming and unsuccessful, and third parties maychallenge the validity or enforceability of our patents and they may be successful,” and Part I, Item 3, Legal Proceedings, of this annual report on Form 10-Kfor additional information. See also Note 16, Legal Matters, to the consolidated financial statements included in Part II of this annual report on Form 10-K for44Table of Contentsadditional information. Eight additional U.S. patents directed to methods of treating patients with Fanapt®, which are set to expire between 2025 and 2031,were issued to us in 2015.A directive in the E.U. provides that companies that receive regulatory approval for a new medicinal product will have a 10-year period of marketexclusivity for that product (with the possibility of a further one-year extension), beginning on the date of such European regulatory approval, regardless ofwhen the European NCE patent covering such product expires. A generic version of the approved drug may not be marketed or sold in Europe during suchmarket exclusivity period. This directive is of material importance with respect to Fanapt®, since the European NCE patent for Fanapt® has expired.Assuming we gain a five-year patent term restoration for tradipitant, and that we continue to have rights under our license agreement with respect tothis product, we would have exclusive rights to tradipitant’ s U.S. NCE patent until 2029. Assuming we gain a five-year patent term restoration for VQW-765,and that we continue to have rights under our license agreement with respect to this product, we would have exclusive rights to VQW-765’s U.S. NCE patentuntil 2028.However, there is no assurance that we will receive the extensions of our patents or other exclusive rights available under the Hatch-Waxman Act orsimilar foreign legislation. If we fail to receive such extensions or exclusive rights, our ability to prevent competitors from manufacturing, marketing andselling generic versions of our products will be materially impaired.We may not be successful in the development of products for our own account.In addition to our business strategy of acquiring rights to develop and commercialize products, we may develop products for our own account byapplying our technologies to off-patent drugs as well as developing our own proprietary molecules. Because we will be funding the development of suchprograms, there is a risk that we may not be able to continue to fund all such programs to completion or to provide the support necessary to perform theclinical trials, obtain regulatory approvals or market any approved products. We expect the development of products for our own account to consumesubstantial resources. If we are able to develop commercial products on our own, the risks associated with these programs may be greater than thoseassociated with our programs with collaborative partners.Litigation or third-party claims of intellectual property infringement could require us to divert resources and may prevent or delay our drug discoveryand development efforts.Our commercial success depends in part on our not infringing the patents and proprietary rights of third parties. Third parties may assert that we areemploying their proprietary technology without authorization. In addition, third parties may obtain patents in the future and claim that use of ourtechnologies infringes upon these patents.Furthermore, parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to developand commercialize one or more of our products. Defense of these claims, regardless of their merit, would divert substantial financial and employee resourcesfrom our business. In the event of a successful claim of infringement against us, we may have to pay substantial damages, obtain one or more licenses fromthird parties or pay royalties. In addition, even in the absence of litigation, we may need to obtain additional licenses from third parties to advance ourresearch or allow commercialization of our products. We may fail to obtain any of these licenses at a reasonable cost or on reasonable terms, if at all. In thatevent, we would be unable to develop and commercialize further one or more of our products.In addition, in the future we could be required to initiate litigation to enforce our proprietary rights against infringement by third parties.Prosecution of these claims to enforce our rights against others could divert substantial financial and employee resources from our business. If we fail toenforce our proprietary rights against others, our business will be harmed.As described elsewhere in these risk factors and in Part I, Item 3, Legal Proceedings, of this annual report on Form 10-K, we have initiated lawsuits toenforce our patent rights against certain generic pharmaceutical companies.Risks related to our common stockOur stock price has been highly volatile and may be volatile in the future, and purchasers of our common stock could incur substantial losses.The realization of any of the risks described in these risk factors or other unforeseen risks could have a dramatic and adverse effect on the marketprice of our common stock. Between January 1, 2018 and December 31, 2018, the high and low sale prices of our common stock as reported on The NasdaqGlobal Market varied between $13.75 and $33.44. Additionally, market prices for securities of biotechnology and pharmaceutical companies, including ours,have historically been very45Table of Contentsvolatile. The market for these securities has from time to time experienced significant price and volume fluctuations for reasons that were unrelated to theoperating performance of any one company.The following factors, in addition to the other risk factors described in this section, may also have a significant impact on the market price of ourcommon stock: •our level of success in commercializing our products;•our level of success in executing our commercialization strategies;•publicity regarding actual or potential testing or trial results relating to products under development by us or our competitors;•the outcome of regulatory review relating to products under development by us or our competitors;•regulatory developments in the U.S. and foreign countries;•developments concerning any collaboration or other strategic transaction we may undertake;•publicity regarding actual or potential litigation involving us;•announcements of patent issuances or denials, technological innovations or new commercial products by us or our competitors;•safety issues with our products or those of our competitors;•announcements of technological innovations or new therapeutic products or methods by us or others;•actual or anticipated variations in our quarterly operating results;•changes in estimates of our financial results or recommendations by securities analysts or failure to meet such financial expectations;•changes in government regulations or policies;•changes in patent legislation or patent decisions or adverse changes to patent law;•additions or departures of key personnel or members of our board of directors;•the publication of negative research or articles about our company, our business or our products by industry analysts or others;•market rumors or press reports;•publicity regarding actual or potential transactions involving us; and•economic, political and other external factors beyond our control.We have been and may in the future be subject to litigation, which could harm our stock price, business, results of operations and financial condition.We have been the subject of litigation in the past and may be subject to litigation in the future. In the past, following periods of volatility in themarket price of their stock, many companies, including us, have been the subjects of securities class action litigation. Any such litigation can result insubstantial costs and diversion of management’s attention and resources and could harm our stock price, business results of operations and financialcondition. As a result of these factors, holders of our common stock might be unable to sell their shares at or above the price they paid for such shares.If there are substantial sales of our common stock, our stock price could decline.A small number of institutional investors and private equity funds hold a significant number of shares of our common stock. Sales by thesestockholders of a substantial number of shares, or the expectation of such sales, could cause a significant reduction in the market price of our common stock.In addition to our outstanding common stock, as of December 31, 2018 there were a total of 5,682,618 shares of our common stock that we haveregistered and that we are obligated to issue upon the exercise of currently outstanding options and settlement of restricted stock unit awards granted underour 2006 and 2016 Equity Incentive Plans. Upon the exercise of these options or settlement of the shares underlying these restricted stock units, as the casemay be, in accordance with their respective terms, these shares may be resold freely, subject to restrictions imposed on our affiliates under Rule 144. If46Table of Contentssignificant sales of these shares occur in short periods of time, these sales could reduce the market price of our common stock. Any reduction in the tradingprice of our common stock could impede our ability to raise capital on attractive terms, if at all.If we fail to maintain the requirements for continued listing on The Nasdaq Global Market, our common stock could be delisted from trading, whichwould adversely affect the liquidity of our common stock and our ability to raise additional capital.Our common stock is currently listed for quotation on The Nasdaq Global Market. We are required to meet specified listing criteria in order tomaintain our listing on The Nasdaq Global Market. If we fail to satisfy The Nasdaq Global Market’s continued listing requirements, our common stock couldbe delisted from The Nasdaq Global Market, in which case we may transfer to The Nasdaq Capital Market, which generally has lower financial requirementsfor initial listing or, if we fail to meet its listing requirements, the over-the-counter bulletin board. Any potential delisting of our common stock from TheNasdaq Global Market would make it more difficult for our stockholders to sell our stock in the public market and would likely result in decreased liquidityand increased volatility for our common stock.If securities or industry analysts do not publish research or reports or publish unfavorable research about our business, our stock price and tradingvolume could decline.The trading market for our common stock will depend in part on the research and reports that securities or industry analysts publish about us or ourbusiness. We currently have research coverage by securities and industry analysts. If one or more of the analysts who covers us downgrades our stock, ourstock price would likely decline. If one or more of these analysts ceases coverage of our Company or fails to regularly publish reports on us, interest in thepurchase of our stock could decrease, which could cause our stock price or trading volume to decline.Our common stock may experience future dilution as a result of future equity offerings.In order to raise additional capital, we may in the future offer additional shares of our common stock or other securities convertible into orexchangeable for our common stock at prices that may not be the same as the price per share in previous offerings. We may sell shares or other securities inany other offering at a price per share that is less than the price per share paid by investors in previous offerings, and investors purchasing shares or othersecurities in the future could have rights superior to existing stockholders. The price per share at which we sell additional shares of our common stock, orsecurities convertible or exchangeable into common stock, in future transactions may be higher or lower than the price per share paid by investors.Our business could be negatively affected as a result of the actions of activist stockholders.Proxy contests have been waged against many companies in the biopharmaceutical industry, including us, over the last several years. If faced with aproxy contest or other type of shareholder activism, we may not be able to respond successfully to the contest or dispute, which would be disruptive to ourbusiness. Even if we are successful, our business could be adversely affected by a proxy contest or shareholder dispute involving us because: •responding to proxy contests and other actions by activist stockholders can be costly and time-consuming, disrupting operations and divertingthe attention of management and employees;•perceived uncertainties as to future direction may result in the loss of potential acquisitions, collaborations or in-licensing opportunities, andmay make it more difficult to attract and retain qualified personnel and business partners; and•if individuals are elected to a board of directors with a specific agenda, it may adversely affect our ability to effectively and timely implementour strategic plan and create additional value for our stockholders.These actions could cause our stock price to experience periods of volatility.Anti-takeover provisions in our charter and bylaws and under Delaware law, and the adoption of a rights plan, could prevent or delay a change incontrol of our company.We are a Delaware corporation and the anti-takeover provisions of Section 203 of the Delaware General Corporation Law may discourage, delay orprevent a change in control by prohibiting us from engaging in a business combination with an interested stockholder for a period of three years after theperson becomes an interested stockholder, even if a change of control would be beneficial to our existing stockholders. In addition, our amended and restatedcertificate of incorporation and bylaws47Table of Contentsmay discourage, delay or prevent a change in our management or control over us that stockholders may consider favorable. Our amended and restatedcertificate of incorporation and bylaws:•authorize the issuance of “blank check” preferred stock that could be issued by our board of directors to thwart a takeover attempt;•do not provide for cumulative voting in the election of directors, which would allow holders of less than a majority of the stock to elect somedirectors;•establish a classified board of directors, as a result of which the successors to the directors whose terms have expired will be elected to serve fromthe time of election and qualification until the third annual meeting following their election;•require that directors only be removed from office for cause;•provide that vacancies on the board of directors, including newly-created directorships, may be filled only by a majority vote of directors thenin office;•limit who may call special meetings of stockholders;•prohibit stockholder action by written consent, requiring all actions to be taken at a meeting of the stockholders; and•establish advance notice requirements for nominating candidates for election to the board of directors or for proposing matters that can be actedupon by stockholders at stockholder meetings.Our board of directors previously adopted a rights agreement, the provisions of which could have had the effect of discouraging, delaying orpreventing a change in or management or control over us. While there is no plan to do so at this time, our board of directors may choose to adopt a newrights plan in the future.Global economic conditions may have an adverse effect on our business.Financial instability or a general decline in economic conditions in the U.S. and other countries where we sell our product could adversely affect ouroperations. Economic conditions, and uncertainty as to the general direction of the macroeconomic environment, are beyond our control and may make anynecessary debt or equity financing more difficult, more costly, and more dilutive. While we believe we have adequate capital resources to meet currentworking capital and capital expenditure requirements, an economic downturn or significant increase in our expenses could require additional financing onless than attractive rates or on terms that are excessively dilutive to existing stockholders. Failure to secure any necessary financing in a timely manner andon favorable terms could have a material adverse effect on our stock price and could require us to delay or abandon clinical development plans.Sales of our products will be dependent, in large part, on reimbursement from government health administration authorities, private health insurers,distribution partners and other organizations. In the event of economic decline, these organizations may be unable to satisfy their reimbursement obligationsor may delay payment. In addition, federal and state health authorities may reduce Medicare and Medicaid reimbursements, and private insurers may increasetheir scrutiny of claims. A reduction in the availability or extent of reimbursement could negatively affect our product sales and revenue.In addition, we rely on third parties for several important aspects of our business. For example, we use third parties for sales, distribution, medicalaffairs and clinical research, and we rely upon several single source providers of raw materials and contract manufacturers for the manufacture of our products.During challenging and uncertain economic times and in tight credit markets, there may be a disruption or delay in the performance of our third partycontractors, suppliers or partners. If such third parties are unable to satisfy their commitments to us, our business and results of operations would be adverselyaffected.ITEM 1B.UNRESOLVED STAFF COMMENTSNot applicable.48Table of ContentsITEM 2.PROPERTIESOur headquarters office consists of a total of 43,462 square feet of office space located at 2200 Pennsylvania Avenue, N.W. in Washington, D.C.under operating leases and subleases that expire between 2026 and 2028 and are subject to renewal options. In addition, we have 2,880 square feet of officespace for our European headquarters in London under an operating lease that has a lease term ending in 2021 and is subject to a renewal option, and 1,249square feet of office space in Berlin under a short-term operating lease. We believe that these facilities are suitable and adequate to meet our anticipated near-term needs. We anticipate that following the expiration of the leases, additional or alternative space will be available at commercially reasonable terms.ITEM 3.LEGAL PROCEEDINGSFanapt®. In June 2014, we filed suit against Roxane Laboratories, Inc. (Roxane) in the U.S. District Court for the District of Delaware (DelawareDistrict Court). The suit sought an adjudication that Roxane has infringed one or more claims of our U.S. Patent No. 8,586,610 (‘610 Patent) by submitting tothe U.S. Food and Drug Administration (FDA) an Abbreviated New Drug Application (ANDA) for a generic version of Fanapt® prior to the expiration of the‘610 Patent in November 2027. In addition, pursuant to a settlement agreement with Novartis Pharma AG (Novartis), we assumed Novartis’ patentinfringement action against Roxane in the Delaware District Court. That suit alleges that Roxane has infringed one or more claims of U.S. Patent RE39198(‘198 Patent), which is licensed exclusively to us, by filing an ANDA for a generic version of Fanapt® prior to the expiration of the ‘198 Patent in November2016. These two cases against Roxane were consolidated by agreement of the parties and were tried together in a five-day bench trial that concluded inMarch 2016. In August 2016, the Delaware District Court ruled that we are entitled to a permanent injunction against Roxane enjoining Roxane frominfringing the ‘610 Patent, including the manufacture, use, sale, offer to sell, sale, distribution or importation of any generic iloperidone product described inthe ‘610 Patent ANDA until the expiration of the ‘610 Patent in November 2027. If we obtain pediatric exclusivity, the injunction against Roxane would beextended until May 2028 under the Delaware District Court’s order. In September 2016, Roxane filed a notice of appeal with the Federal Circuit Court ofAppeals (Federal Circuit). In July 2017, Roxane, now a subsidiary of Hikma Pharmaceuticals PLC (Hikma), petitioned the Federal Circuit to substituteRoxane with new defendants West-Ward Pharmaceuticals International Limited and West-Ward Pharmaceuticals Corp. (each of which is a subsidiary ofHikma and both of which are referred to collectively herein as West-Ward). In April 2018, the Federal Circuit affirmed the Delaware District Court’s decisionthat West-Ward infringed the ‘610 Patent. In June 2018, West-Ward filed with the Federal Circuit a petition seeking rehearing en banc. The Federal Circuitinvited us to respond to West-Ward’s petition; our response was filed in July 2018. In August 2018, the Federal Circuit denied West-Ward's petition forrehearing. In January 2019, West-Ward filed a petition in the United States Supreme Court for a writ of certiorari seeking reversal of the Federal Circuit’sdecision. We submitted a response to that petition on February 12, 2019.In 2015, we filed six separate patent infringement lawsuits in the Delaware District Court against Roxane, Inventia Healthcare Pvt. Ltd. (Inventia),Lupin Ltd. and Lupin Pharmaceuticals, Inc. (Lupin), Taro Pharmaceuticals USA, Inc. and Taro Pharmaceutical Industries, Ltd. (Taro), and Apotex Inc. andApotex Corp. (Apotex, and collectively with Roxane, Inventia, Lupin and Taro, the Defendants). The lawsuits each seek an adjudication that the respectiveDefendants infringed one or more claims of the ‘610 Patent and/or our U.S. Patent No. 9,138,432 (‘432 Patent) by submitting to the FDA an ANDA for ageneric version of Fanapt® prior to the expiration of the ‘610 Patent in November 2027 or the ‘432 Patent in September 2025. The Defendants deniedinfringement and counterclaimed for declaratory judgment of invalidity and noninfringement of the ‘610 Patent and the ‘432 Patent. Certain Defendantshave since entered into agreements resolving these lawsuits, as discussed below. The remaining matters have been stayed until the later of November 30,2018 or 14 days after final disposition by the U.S. Supreme Court of any petition for a writ of certiorari filed by West-Ward. We entered into a confidentialstipulation with each of Inventia and Lupin regarding any potential launch of Inventia’s and Lupin's generic ANDA products.Lupin filed counter claims for declaratory judgment of invalidity and noninfringement of seven of our method of treatment patents that are listed inthe Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) related to Fanapt® (such seven patents, the Method of TreatmentPatents). We have not sued Lupin for infringing the Method of Treatment Patents. In October 2016, we, along with Lupin, filed a Stipulation of Dismissal inthe Delaware District Court pursuant to which Lupin’s counterclaims relating to the Method of Treatment Patents were dismissed without prejudice inrecognition of an agreement reached between the parties by which we would not assert those patents against Lupin absent certain changes in Lupin’sproposed prescribing information for its iloperidone tablets.Taro and Apotex each entered into separate License Agreements (together, the License Agreements) resolving these lawsuits in October 2016 andDecember 2016, respectively. The License Agreements grant Taro and Apotex non-exclusive49Table of Contentslicenses to manufacture and commercialize a version of Fanapt® in the U.S. effective November 2027, unless prior to that date we obtain pediatric exclusivityfor Fanapt®, in which case, the license will be effective May 2028. Taro and Apotex each may enter the market earlier under certain limited circumstances.The License Agreements, which are subject to review by the U.S. Federal Trade Commission (FTC) and the U.S. Department of Justice (DOJ), provide for a fullsettlement and release of all claims that are the subject of the respective litigation with Taro and Apotex.In February 2016, Roxane filed suit against us in the U.S. District Court for the Southern District of Ohio (Ohio District Court). The suit sought adeclaratory judgment of invalidity and noninfringement of the Method of Treatment Patents. In December 2016, the Ohio District Court dismissed Roxane’ssuit without prejudice for lack of personal jurisdiction.In February 2016, Roxane filed a Petition for Inter Partes Review (IPR) of the ‘432 Patent with the Patent Trials and Appeals Board (PTAB) of theU.S. Patent and Trademark Office. In August 2016, the PTAB denied the request by Roxane to institute an IPR of the ‘432 Patent. In September 2016, Roxanefiled a Petition for Rehearing with the PTAB. In November 2016, the PTAB denied Roxane’s Petition for Rehearing.HETLIOZ®. In March 2018, we received a Paragraph IV certification notice letter from Teva Pharmaceuticals USA, Inc. (Teva) notifying us that Tevahad submitted an ANDA for HETLIOZ® to the FDA requesting approval to market, sell and use a generic version of the 20mg HETLIOZ® capsules for Non-24-Hour-Sleep-Wake Disorder. In its notice letter, Teva alleges that our Orange Book listed U.S. Patent No. RE46,604, U.S. Patent No. 9,060,995, U.S. Patent9,539,234, U.S. Patent 9,549,913, U.S. Patent 9,730,910 and U.S. Patent 9,885,241 (collectively, the Vanda Patents), which cover methods of usingHETLIOZ®, are invalid, unenforceable and/or will not be infringed by Teva’s manufacture, use or sale of the product described in its ANDA. We receivedsimilar notice letters in April 2018 from MSN Pharmaceuticals Inc. and MSN Laboratories Private Limited (together, MSN) and Apotex.In April 2018, we filed a patent infringement lawsuit in the Delaware District Court against Teva and in May 2018, we filed patent infringementlawsuits in the Delaware District Court against MSN and Apotex. The lawsuits seek an adjudication that Teva, MSN and Apotex have infringed one or moreclaims of the Vanda Patents by submitting to the FDA an ANDA for a generic version of HETLIOZ® prior to the expiration of the latest to expire of the VandaPatents in 2034. The relief requested by us in the lawsuits includes requests for permanent injunctions preventing Teva, MSN and Apotex from infringing theasserted claims of the Vanda Patents by engaging in the manufacture, use, offer to sell, sale, importation or distribution of generic versions of HETLIOZ®before the last expiration date of the Vanda Patents and for an order that any effective date of FDA approval of Teva, MSN, and Apotex’s generic versions ofHETLIOZ® be a date not earlier than the expiration of the Vanda Patents. The lawsuits automatically preclude the FDA from approving the submitted ANDAsuntil the earlier of seven and one-half years after the January 2014 approval of our application for New Chemical Entity Status or entry of a district courtdecision finding the Vanda Patents invalid, unenforceable or not infringed. In June 2018, Teva, MSN and Apotex each answered our complaint, and Tevaincluded counterclaims for declarations that the Vanda Patents are invalid. MSN included additional counterclaims for declarations that the Vanda Patentsare not infringed. In July 2018, we answered Teva and MSN's counterclaims, denying their allegations.In October 2018, we received an additional Paragraph IV certification notice letter from Teva concerning our Orange Book listed U.S. Patent No.10,071,977, which expires in 2035 (the ‘977 Patent). In November 2018, we received a similar additional Paragraph IV certification notice letter from Apotexconcerning the ’977 Patent. In December 2018, we filed amended complaints against Teva, Apotex, and MSN alleging infringement of one or more claims ofthe ’977 Patent. The amended complaints seek an adjudication that Teva, Apotex, and MSN have infringed one or more claims of the ’977 Patent bysubmitting to FDA an ANDA for a generic version of HETLIOZ® prior to the expiration of the ’977 Patent. The relief requested by us in the amendedcomplaints includes requests for permanent injunctions preventing Teva, Apotex, and MSN from infringing the asserted claims of the ’977 Patent byengaging in the manufacture, use, offer to sell, sale, importation or distribution of generic versions of HETLIOZ® before the expiration date of the ’977 Patentand for an order that any effective date of FDA approval of Teva, MSN, and Apotex’s generic versions of HETLIOZ® be a date not earlier than the expirationof the ’977 Patent. In December 2018, Teva, MSN, and Apotex answered our amended complaints, and Teva and MSN included counterclaims fordeclarations that the ’977 Patent is invalid, and MSN included an additional counterclaim that the ’977 Patent is unenforceable for inequitable conduct. InJanuary 2019, we answered Teva and MSN’s counterclaims. A trial date for these lawsuits has been set for September 2020.In February 2019, we received an additional Paragraph IV certification notice letter from Teva concerning our Orange Book listed U.S. Patent No.10,149,829, which expires in 2033 (the ’829 Patent). In its notice letter, Teva alleges that the ’829 Patent, which covers methods of using HETLIOZ®, isinvalid, unenforceable and will not be infringed by Teva’s manufacture, use or sale of the product described in its ANDA.50Table of ContentsOther Matters. In April 2018, we submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) period for patientswho had completed the tradipitant Phase II clinical study (2301) in gastroparesis. In May 2018, based on feedback from the FDA, we amended the protocollimiting the duration of treatment in the 2301 study to a total of three months, while continuing to seek further dialogue with the FDA on extending the studyduration to 52-weeks. As a part of this negotiation process, in September 2018, we submitted a new follow-on 52-week OLE protocol to the FDA (2302) forpatients who had completed the 2301 study. While waiting for further feedback, no patients were ever enrolled in any study beyond 12 weeks. On December19, 2018, the FDA imposed a partial clinical hold (PCH) on the two proposed studies, stating that we are required first to conduct additional chronic toxicitystudies in canines, monkeys or minipigs before allowing patients access in any clinical protocol beyond 12 weeks. The PCH was not based on any safety orefficacy data related to tradipitant. Rather, the FDA informed us that these additional toxicity studies are required by a guidance document. We believe thatthe FDA does not have legal authority to issue the PCH on the basis of the guidance at issue. We also believe that we have provided the FDA with sufficientinformation regarding the safety of tradipitant to justify the continued study of tradipitant in patients beyond 12 weeks, in accordance with applicable lawand FDA regulations. On February 5, 2019, we filed a lawsuit against the FDA in the U.S. District Court for the District of Columbia (DC District Court),challenging the FDA’s legal authority to issue the PCH, and seeking an order to set it aside. On February 14, 2019, the FDA filed a Motion for VoluntaryRemand to the Agency and for a Stay of the Case. We intend to continue vigorously pursuing our interests in the matter. The PCH and Vanda’s plans fortradipitant clinical development are discussed in greater detail in Part I, Item 1, Business, of this annual report on Form 10-K.On February 4, 2019, a qui tam action filed against us was unsealed by order of the DC District Court entered on January 31, 2019. The qui tamaction, United States ex rel. Richard Gardner v. Vanda Pharmaceuticals Inc., which was filed under seal on March 10, 2017, was brought by one of our formeremployees on behalf of the U.S., 28 states and the District of Columbia (collectively, the Plaintiff States) and the policyholders of certain insurancecompanies under the Federal False Claims Act and state law equivalents to the Federal False Claims Act and related state laws. The complaint alleges that theCompany violated these laws through the promotion and marketing of its products Fanapt® and HETLIOZ®. The complaint seeks, among other things, trebledamages, civil penalties for each alleged false claim, and attorneys’ fees and costs.We have not been served with the qui tam complaint. By virtue of the court having unsealed the case, we learned that on January 29, 2019, theUnited States, as well as the Plaintiff States, filed notice of their election not to intervene in the qui tam action at this time. The U.S.’ and the Plaintiff States’election not to intervene does not prevent the plaintiff/relator from litigating this action and the U.S. and the Plaintiff States may later seek to intervene in theaction. We intend to vigorously defend ourselves in the litigation if served.ITEM 4.MINE SAFETY DISCLOSURESNot applicable.PART II ITEM 5.MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OFEQUITY SECURITIESOur common stock is quoted on The Nasdaq Global Market under the symbol “VNDA.” As of February 12, 2019, there were 7 holders of record ofour common stock. The number of holders of record of our common stock does not reflect the number of beneficial holders whose shares are held bydepositors, brokers or other nominees.Market Price of and Dividends on the Registrant’s Common Equity and Related Stockholder MattersThe following graph shows the cumulative five-year total return on our common stock relative to the cumulative total returns of the NasdaqComposite Index and the Nasdaq Biotechnology Index. An investment of $100 (with reinvestment of dividends) is assumed to have been made in ourcommon stock and in each of the indexes on December 31, 2013 and its relative performance is tracked through December 31, 2018. The comparisons in thetable are required by the Securities and Exchange Commission (SEC) and are not intended to forecast or be indicative of possible future performance of ourcommon stock. We have not paid dividends to our stockholders since the inception (other than a dividend of preferred share purchase rights which wasdeclared in September 2008) and do not plan to pay dividends in the foreseeable future. The following graph and related information is being furnishedsolely to accompany this annual report on Form 10-K pursuant to Item 201(e) of Regulation S-K and shall not be deemed “soliciting materials” or to be“filed” with the SEC (other than as provided in51Table of ContentsItem 201), nor shall such information be incorporated by reference into any of our filings under the Securities Act of 1933, as amended, or the SecuritiesExchange Act of 1934, as amended, whether made before or after the date hereof, and irrespective of any general incorporation language in any such filing.Securities Authorized for Issuance under Equity Incentive PlansInformation regarding securities authorized for issuance under equity incentive plans will be contained in our Proxy Statement for the 2019 AnnualMeeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year ended December 31, 2018, under the captions “EquityCompensation Plan Information” and “Security Ownership of Certain Beneficial Owners and Management” and is incorporated herein by reference pursuantto General Instruction G (3) to Form 10-K.52Table of ContentsITEM 6.SELECTED CONSOLIDATED FINANCIAL DATAThe consolidated statements of operations data for the years ended December 31, 2018, 2017 and 2016 and the consolidated balance sheet data as ofDecember 31, 2018 and 2017 are each derived from our audited consolidated financial statements included in this annual report on Form 10-K. Theconsolidated statements of operations data for the years ended December 31, 2015 and 2014, and the consolidated balance sheet data as of December 31,2016, 2015 and 2014 are each derived from our audited consolidated financial statements not included herein. Our historical results for any prior period arenot necessarily indicative of results to be expected in any future period.The following data should be read together with our consolidated financial statements and accompanying notes and the section entitledManagement’s Discussion and Analysis of Financial Condition and Results of Operations included in this annual report on Form 10-K. Year Ended December 31,(in thousands, except for share and per share amounts)2018 (1) 2017 (1) 2016 (1) 2015 (1) 2014 (1)(2)Statements of Operations Data Total revenues$193,118 $165,083 $146,017 $109,925 $50,157Operating expenses: Cost of goods sold excluding amortization20,508 17,848 24,712 23,462 1,583Research and development43,594 38,547 29,156 29,145 19,230Selling, general and administrative105,751 123,841 99,787 84,531 84,644Intangible asset amortization1,527 1,750 10,933 12,972 2,254Gain on arbitration settlement— — — — (77,616)Total operating expenses171,380 181,986 164,588 150,110 30,095Income (loss) from operations21,738 (16,903) (18,571) (40,185) 20,062Other income3,608 1,472 665 320 124Income (loss) before income taxes25,346 (15,431) (17,906) (39,865) 20,186Provision for income taxes138 136 104 — —Net income (loss)$25,208 $(15,567) $(18,010) $(39,865) $20,186Net income (loss) per share: Basic$0.50 $(0.35) $(0.41) $(0.94) $0.58Diluted$0.48 $(0.35) $(0.41) $(0.94) $0.55Weighted average shares outstanding: Basic50,859,947 44,735,146 43,449,441 42,250,254 34,774,163Diluted53,045,257 44,735,146 43,449,441 42,250,254 36,686,723 December 31, 2018 2017 2016 2015 2014Balance Sheet Data Cash and cash equivalents$61,005 $33,627 $40,426 $50,843 $60,901Marketable securities196,355 109,786 100,914 92,337 68,921Working capital246,117 99,494 123,855 115,230 133,944Total assets332,130 205,425 210,374 213,050 171,704Total liabilities56,708 74,038 79,044 80,023 10,887Accumulated deficit(336,218) (361,426) (345,859) (327,849) (287,984)Total stockholders’ equity275,422 131,387 131,330 133,027 160,817 (1)We adopted Accounting Standards Codification (ASC) Subtopic 606 Revenue from Contracts with Customers (ASC 606), effective January 1, 2018,using the modified retrospective method to those contracts which were not completed as of January 1, 2018. Results for the years ended December31, 2017, 2016, 2015 and 2014 are accounted for in accordance with ASC 605.53Table of Contents(2)Net income for the year ended December 31, 2014 includes a gain on arbitration settlement of $77.6 million, or $2.23 and $2.12 per basic anddiluted share, respectively.54Table of ContentsITEM 7.MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONSYou should read the following discussion and analysis of our financial condition and results of operations together with Selected ConsolidatedFinancial Data and our consolidated financial statements and related notes appearing in this annual report on Form 10-K. Some of the informationcontained in this discussion and analysis or set forth elsewhere in this annual report on Form 10-K include historical information and other informationwith respect to our plans and strategy for our business and contain forward-looking statements that involve risks, uncertainties and assumptions. Ouractual results may differ materially from those anticipated in these forward-looking statements as a result of certain factors, including but not limited tothose set forth under the “Risk Factors” section of this report and elsewhere in this annual report on Form 10-K.OverviewVanda Pharmaceuticals Inc. (we, our or Vanda) is a global biopharmaceutical company focused on the development and commercialization ofinnovative therapies to address high unmet medical needs and improve the lives of patients. We commenced operations in 2003 and our product portfolioincludes: •HETLIOZ® (tasimelteon), a product for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24), was approved by the U.S. Food and DrugAdministration (FDA) in January 2014 and launched commercially in the U.S. in April 2014. In July 2015, the European Commission (EC)granted centralized marketing authorization with unified labeling for HETLIOZ® for the treatment of Non-24 in totally blind adults. HETLIOZ®was commercially launched in Germany in August 2016. HETLIOZ® has potential utility in a number of other circadian rhythm disorders and ispresently in clinical development for the treatment of jet lag disorder, Smith-Magenis Syndrome (SMS) and Pediatric Non-24. An assessment ofnew HETLIOZ® clinical opportunities including the treatment of delayed sleep phase disorder and for sleep disorders in patients withneurodevelopmental disorders is ongoing.•Fanapt® (iloperidone), a product for the treatment of schizophrenia, the oral formulation of which was approved by the FDA in May 2009 andlaunched commercially in the U.S. by Novartis Pharma AG (Novartis) in January 2010. Novartis transferred all the U.S. and Canadiancommercial rights to the Fanapt® franchise to us on December 31, 2014. Additionally, our distribution partners launched Fanapt® in Israel in2014. Fanapt® has potential utility in a number of other disorders. Initial clinical work studying a long acting injectable (LAI) formulation ofFanapt® began in 2018. An assessment of new Fanapt® clinical opportunities including the treatment of bipolar depression is ongoing.•Tradipitant (VLY-686), a small molecule neurokinin-1 receptor (NK-1R) antagonist, which is presently in clinical development for the treatmentof chronic pruritus in atopic dermatitis and the treatment of gastroparesis. An assessment of new tradipitant clinical opportunities including thetreatment of motion sickness is ongoing.•VTR-297, a small molecule histone deacetylase (HDAC) inhibitor presently in clinical development for the treatment of hematologicmalignancies.•Portfolio of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activators and inhibitors. An early stage CFTR activator program isplanned for the treatment of dry eye and ocular inflammation. In addition, an early stage CFTR inhibitor program is planned for the treatment ofsecretory diarrhea disorders, including cholera.•VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist.Operational HighlightsTradipitant - Clinical Development•In December 2018, we announced positive results from a Phase II clinical study (2301) of tradipitant in gastroparesis. Gastroparesis patients treatedwith tradipitant demonstrated significant improvement in nausea and most of the core gastroparesis symptoms.•We expect to meet with the FDA to further define and confirm the path towards approval of tradipitant in the treatment of patients with gastroparesis,including the planned initiation of a Phase III clinical study in the second quarter of 2019.•Enrollment in the Phase III clinical study (EPIONE) of tradipitant in atopic dermatitis is ongoing. Results are expected in the first half of 2020. Asecond Phase III clinical study is expected to begin in the first quarter of 2020.55Table of Contents•In January 2019, we initiated a Phase II clinical study of tradipitant in motion sickness. Study results are expected in the second quarter of 2019.HETLIOZ® •In December 2018, we announced positive results from a clinical study of HETLIOZ® in SMS. SMS patients treated with HETLIOZ® demonstratedsignificant improvement in overall sleep quality and overall total nighttime sleep duration.•We expect to meet with the FDA in the second quarter of 2019 to confirm the regulatory path forward for HETLIOZ® in the treatment of patients withSMS and expects to file a supplemental New Drug Application (sNDA) in the third quarter of 2019.•In December 2018, we announced that the FDA had accepted the HETLIOZ® sNDA for the treatment of jet lag disorder with a Prescription Drug UserFee Act target action date of August 16, 2019.•We plan in the third quarter of 2019 to initiate a Phase II clinical study of HETLIOZ® in delayed sleep phase disorder (DSPD) in patients who have amutation in the CRY1 gene which is believed to be causative in a subset of patients with the disorder.Fanapt® •Enrollment is ongoing in a pharmacokinetic study for the LAI formulation of Fanapt®. A randomized clinical study of the LAI formulation inschizophrenia is planned to begin in 2019.•A randomized study of Fanapt® in bipolar disorder is planned to begin in 2019.VTR-297•Enrollment is ongoing in a Phase I clinical study (1101) of VTR-297 in hematologic malignancies.Tradipitant - Partial Clinical Hold and FDA Dispute•In April 2018, we submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) period for patients who hadcompleted the tradipitant Phase II clinical study (2301) in gastroparesis. In May 2018, based on feedback from the FDA, we amended the protocollimiting the duration of treatment in the 2301 study to a total of three months, while continuing to seek further dialogue with the FDA on extendingthe study duration to 52-weeks. As a part of this negotiation process, in September 2018, we submitted a new follow-on 52-week OLE protocol to theFDA (2302) for patients who had completed the 2301 study. While waiting for further feedback, no patients were ever enrolled in any study beyond12 weeks.•On December 19, 2018, the FDA imposed a partial clinical hold (PCH) on the two proposed studies, stating that we are required first to conductadditional chronic toxicity studies in canines, monkeys or minipigs before allowing patients access in any clinical protocol beyond 12 weeks. ThePCH was not based on any safety or efficacy data related to tradipitant. Rather, the FDA informed us that these additional toxicity studies arerequired by a guidance document.•On February 5, 2019, we filed a lawsuit against the FDA in the United States District Court for the District of Columbia, challenging the FDA’s legalauthority to issue the PCH, and seeking an order to set it aside (see Part I, Item 3, Legal Proceedings of this annual report on Form 10-K foradditional information).•We do not expect the PCH to have any material impact on our ongoing clinical studies in atopic dermatitis and motion sickness or the plannedPhase III study in gastroparesis. At present, the PCH has not had any impact on the potential timing of an NDA filing or approval for theseindications. We will continually reassess this situation as events unfold.Since we began operations in March 2003, we have devoted substantially all of our resources to the in-licensing, clinical development andcommercialization of our products. Our ability to generate meaningful product sales and achieve profitability largely depends on our level of success incommercializing HETLIOZ® and Fanapt® in the U.S. and Europe, on our ability, alone or with others, to complete the development of our products, and toobtain the regulatory approvals for and to manufacture, market and sell our products. The results of our operations will vary significantly from year-to-yearand quarter-to-quarter and depend on a number of factors, including risks related to our business, risks related to our industry, and other risks which aredetailed in Risk Factors reported in Item 1A of Part I of this annual report on Form 10-K.56Table of ContentsAs described in Part I, Item 3, Legal Proceedings, of this annual report on Form 10-K, we have initiated lawsuits to enforce our patent rights againstcertain generic pharmaceutical companies.Critical Accounting PoliciesThe preparation of our consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assetsand liabilities and the disclosure of contingent assets and liabilities at the date of our financial statements, as well as the reported revenues and expensesduring the reported periods. We base our estimates on historical experience and on various other factors that we believe are reasonable under thecircumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not apparent from othersources. Actual results may differ from these estimates under different assumptions or conditions.A summary of our significant accounting policies appears in the notes to our audited consolidated financial statements for the year endedDecember 31, 2018 included in this annual report on Form 10-K. However, we believe that the following accounting policies are important to understandingand evaluating our reported financial results, and we have accordingly included them in this discussion.Inventory. Inventory, which is recorded at the lower of cost or net realizable value, includes the cost of third-party manufacturing and other directand indirect costs and is valued using the first-in, first-out method. We capitalize inventory costs associated with our products upon regulatory approvalwhen, based on management’s judgment, future commercialization is considered probable and the future economic benefit is expected to be realized;otherwise, such costs are expensed as research and development. Inventory not expected to be sold within 12 months following the balance sheet date areclassified as non-current.Net Product Sales. Our net product sales consist of sales of HETLIOZ® and sales of Fanapt®. In accordance with Accounting Standards Codification(ASC) Subtopic 606 Revenue from Contracts with Customers (ASC 606), which we adopted January 1, 2018, we account for a contract when it has approvaland commitment from both parties, the rights of the parties are identified, payment terms are identified, the contract has commercial substance andcollectability of consideration is probable. We recognize revenue when control of the product is transferred to the customer in an amount that reflects theconsideration we expect to be entitled to in exchange for those product sales, which is typically once the product physically arrives at the customer. Sales,value add, and usage-based taxes are excluded from revenues.HETLIOZ® is only available in the U.S. for distribution through a limited number of specialty pharmacies, and is not available in retail pharmacies.Fanapt® is available in the U.S. for distribution through a limited number of wholesalers and is available in retail pharmacies. We invoice and record revenuewhen customers, specialty pharmacies and wholesalers, receive product from the third-party logistics warehouse which is the point at which control istransferred to the customer. Revenues and accounts receivable are concentrated with these customers. Outside the U.S., we commercially launchedHETLIOZ® in Germany in August 2016. We have also entered into a distribution agreement with Megapharm Ltd. for the commercialization of Fanapt® inIsrael.The transaction price is determined based upon the consideration to which we will be entitled in exchange for transferring product to the customer.Our product sales are recorded net of applicable discounts, rebates, chargebacks, service fees, co-pay assistance and product returns that are applicable forvarious government and commercial payors. We estimate the amount of variable consideration that should be included in the transaction price utilizing themost likely amount method and update our estimate at each reporting date. Variable consideration is included in the transaction price if, in our judgment, it isprobable that a significant future reversal of cumulative revenue under the contract will not occur. Reserves for variable consideration for rebates,chargebacks and co-pay assistance are based upon the insurance benefits of the end customer, which are estimated using historical activity and, whereavailable, actual and pending prescriptions for which we have validated the insurance benefits. Reserves for variable consideration are classified as productrevenue allowances on the consolidated balance sheets, with the exception of prompt-pay discounts which are classified as reductions of accounts receivable.The reserve for product returns for products that may not be returned for a period of greater than one year from the balance sheet date is classified other non-current liabilities on the consolidated balance sheets. Uncertainties related to variable consideration are generally resolved in the quarter subsequent toperiod end, with the exception of product returns which are resolved during the product expiry period specified in the customer contract. We currently recordsales allowances for the following:Prompt-pay: Specialty pharmacies and wholesalers are offered discounts for prompt payment. We expect that the specialty pharmacies and wholesalerswill earn prompt payment discounts and, therefore, deduct the full amount of these discounts from total product sales when revenues are recognized.57Table of ContentsRebates: Allowances for rebates include mandated and supplemental discounts under the Medicaid Drug Rebate Program as well as contracted rebateprograms with other payors. Rebate amounts owed after the final dispensing of the product to a benefit plan participant are based upon contractualagreements or legal requirements with public sector benefit providers, such as Medicaid. The allowance for rebates is based on statutory or contracteddiscount rates and expected patient utilization.Chargebacks: Chargebacks are discounts that occur when contracted indirect customers purchase directly from specialty pharmacies and wholesalers.Contracted indirect customers, which currently consist primarily of Public Health Service institutions, non-profit clinics, and Federal government entitiespurchasing via the Federal Supply Schedule, generally purchase the product at a discounted price. The specialty pharmacy or wholesaler, in turn, chargesback the difference between the price initially paid by the specialty pharmacy or wholesaler and the discounted price paid to the specialty pharmacy orwholesaler by the contracted customer.Medicare Part D Coverage Gap: Medicare Part D prescription drug benefit mandates manufacturers to fund approximately 50% of the Medicare Part Dinsurance coverage gap for prescription drugs sold to eligible patients through 2018. Public Law No. 115-123, also known as the Bipartisan Budget Actof 2018 enacted on February 9, 2018 increased the manufacturer discount from 50% to 70% effective in 2019 for applicable drugs. We account for theMedicare Part D coverage gap using a point of sale model. Estimates for expected Medicare Part D coverage gap are based in part on historical activityand, where available, actual and pending prescriptions for we have validated the insurance benefits.Service Fees: We receive sales order management, data and distribution services from certain customers. These fees are based on contracted terms and areknown amounts. We accrue service fees at the time of revenue recognition, resulting in a reduction of product sales and the recognition of an accruedliability, unless it is a payment for a distinct good or service from the customer in which case the fair value of those distinct goods or services arerecorded as selling, general and administrative expense.Co-payment Assistance: Patients who have commercial insurance and meet certain eligibility requirements may receive co-payment assistance. Co-payassistance utilization is based on information provided by our third-party administrator.Product Returns: Consistent with industry practice, we generally offer direct customers a limited right to return as defined within our returns policy. Weconsider several factors in the estimation process, including historical return activity, expiration dates of product shipped to specialty pharmacies,inventory levels within the distribution channel, product shelf life, prescription trends and other relevant factors. We do not expect returned goods to beresalable. There was no right of return asset as of December 31, 2018 or 2017.The following table summarizes sales discounts and allowance activity as of and for the years ended December 31, 2018, 2017 and 2016: (in thousands)Rebates &Chargebacks Discounts,Returnsand Other TotalBalances at December 31, 2015$33,423 $3,557 $36,980Provision related to current period sales56,133 19,451 75,584Adjustments for prior period sales(1,842) 790 (1,052)Credits/payments made(56,512) (17,340) (73,852)Balances at December 31, 201631,202 6,458 37,660Provision related to current period sales53,406 23,751 77,157Adjustments for prior period sales(3,883) 1,362 (2,521)Credits/payments made(60,496) (24,214) (84,710)Balances at December 31, 201720,229 7,357 27,586Provision related to current period sales59,317 23,796 83,113Adjustments for prior period sales811 370 1,181Credits/payments made(58,223) (21,823) (80,046)Balances at December 31, 2018$22,134 $9,700 $31,834The provision for rebates and chargebacks of $59.3 million and $53.4 million for the years ended December 31, 2018 and 2017, respectively,primarily represents Medicaid rebates applicable to sales of Fanapt® and HETLIOZ®. The provision for58Table of Contentsdiscounts, returns and other of $23.8 million for each of the years ended December 31, 2018 and 2017, primarily represents wholesaler distribution feesapplicable to sales of Fanapt® and, to a lesser extent, estimated product returns of Fanapt®, as well as co-pay assistance costs and prompt pay discountsapplicable to the sales of both HETLIOZ® and Fanapt®.Stock-based compensation. Compensation costs for all stock-based awards to employees and directors are measured based on the grant date fairvalue of those awards and recognized over the period during which the employee or director is required to perform service in exchange for the award. We usethe Black-Scholes-Merton option pricing model to determine the fair value of stock options. The determination of the fair value of stock options on the dateof grant using an option pricing model is affected by our stock price as well as assumptions regarding a number of complex and subjective variables. Thesevariables include the expected stock price volatility over the expected term of the awards, actual and projected employee stock option exercise behaviors,risk-free interest rate and expected dividends. Expected volatility rates are based on the historical volatility of our publicly traded common stock and otherfactors. The risk-free interest rates are based on the U.S. Treasury yield for a period consistent with the expected term of the option in effect at the time of thegrant. We have not paid dividends to our stockholders since our inception (other than a dividend of preferred share purchase rights which was declared inSeptember 2008) and do not plan to pay dividends in the foreseeable future. As stock-based compensation expense recognized in the consolidated statementsof operations is based on awards ultimately expected to vest, it has been reduced for estimated forfeitures. Forfeitures are estimated at the time of grant andrevised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.Research and development expenses. Research and development expenses consist primarily of fees for services provided by third parties inconnection with the clinical trials, costs of contract manufacturing services for clinical trial use, milestone payments made under licensing agreements priorto regulatory approval, costs of materials used in clinical trials and research and development, costs for regulatory consultants and filings, depreciation ofcapital resources used to develop products, related facilities costs, and salaries, other employee-related costs and stock-based compensation for research anddevelopment personnel. We expense research and development costs as they are incurred for products in the development stage, including manufacturingcosts and milestone payments made under license agreements prior to FDA approval. Upon and subsequent to FDA approval, manufacturing and milestonepayments made under license agreements are capitalized. Milestone payments are accrued when it is deemed probable that the milestone event will beachieved. Costs related to the acquisition of intellectual property are expensed as incurred if the underlying technology is developed in connection with ourresearch and development efforts and has no alternative future use.Clinical trials are inherently complex, often involve multiple service providers, and can include payments made to investigator physicians at studysites. Because billing for services often lags delivery of service by a substantial amount of time, we often are required to estimate a significant portion of ouraccrued clinical expenses. Our assessments include, but are not limited to: (i) an evaluation by the project manager of the work that has been completedduring the period, (ii) measurement of progress prepared internally and/or provided by the third-party service provider, (iii) analyses of data that justify theprogress, and (iv) management’s judgment. In the event that we do not identify certain costs that have begun to be incurred or we under- or over-estimates thelevel of services performed or the costs of such services, our reported expenses for such period would be too low or too high.Selling, general and administrative expenses. Selling, general and administrative expenses consist primarily of salaries, other related costs forpersonnel, including stock-based compensation, related to executive, finance, accounting, information technology, marketing, medical affairs and humanresource functions. Other costs include facility costs not otherwise included in research and development expenses and fees for marketing, medical affairs,legal, accounting and other professional services. Selling, general and administrative expenses also include third party expenses incurred to support sales,business development, and other business activities. Additionally, selling, general and administrative expenses included our estimate for the annual PatientProtection and Affordable Care fee.Intangible Assets. Our intangible assets consist of capitalized license costs for products approved by the FDA. We amortize our intangible assets on astraight-line basis over estimated useful economic life of the related product patents. We assess the impairment of intangible assets whenever events orchanges in circumstances indicate that the carrying value may not be recoverable. Factors we consider important which could trigger an impairment reviewinclude significant underperformance relative to expected historical or projected future operating results, a significant adverse change in legal or regulatoryfactors that could affect the value or patent life including our ability to defend and enforce patent claims and other intellectual property rights and significantnegative industry or economic trends. When we determine that the carrying value of our intangible assets may not be recoverable based upon the existence ofone or more of the indicators of impairment, we measure any impairment based on the amount that carrying value exceeds fair value. No impairments havebeen recognized on our intangible assets.59Table of ContentsIncome taxes. We assess the need for a valuation allowance against its deferred tax asset each quarter through the review of all available positive andnegative evidence. Deferred tax assets are reduced by a tax valuation allowance when, in the opinion of management, it is more likely than not that someportion or all of the deferred tax assets will not be realized. The fact that we have historically generated pretax losses in the U.S. serves as strong evidence thatit is more likely than not that deferred tax assets in the U.S. will not be realized in the future. Therefore, we have recorded a full tax valuation allowanceagainst all net deferred tax assets in the U.S. as of December 31, 2018 and 2017. A reduction of the valuation allowance, in whole or in part, would result in anon-cash income tax benefit during the period of reduction. The potential timing and amount of any future valuation allowance release has yet to bedetermined and requires an analysis that is highly dependent upon historical and future projected earnings, among other factors. Any such adjustment couldhave a material impact our finance position and results of operations.Recent Accounting PronouncementsSee Note 2, Summary of Significant Accounting Policies, to the consolidated financial statements included in Part II of this annual report on Form10-K for information on recent accounting pronouncements.Results of OperationsWe anticipate that our results of operations will fluctuate for the foreseeable future due to several factors, including our and our partners’ ability tosuccessfully commercialize our products, any possible payments made or received pursuant to license or collaboration agreements, progress of our researchand development efforts, the timing and outcome of clinical trials and related possible regulatory approvals. Since our inception, we have incurredsignificant losses resulting in an accumulated deficit of $336.2 million as of December 31, 2018. Our total stockholders’ equity was $275.4 million as ofDecember 31, 2018.Year ended December 31, 2018 compared to year ended December 31, 2017Revenues. Total revenues increased by $28.0 million, or 17%, to $193.1 million for the year ended December 31, 2018 compared to $165.1 millionfor the year ended December 31, 2017. Revenues were as follows: Year Ended December 31,(in thousands)2018 2017 NetChange PercentHETLIOZ® product sales, net$115,835 $89,978 $25,857 29%Fanapt® product sales, net77,283 75,105 2,178 3% $193,118 $165,083 $28,035 17%HETLIOZ® product sales, net increased by $25.9 million, or 29%, to $115.8 million for the year ended December 31, 2018 compared to $90.0million for the year ended December 31, 2017. The increase to net product sales was attributable to an increase in volume and an increase in price net ofdeductions.Fanapt® product sales, net increased by $2.2 million, or 3%, to $77.3 million for the year ended December 31, 2018 compared to $75.1 million forthe year ended December 31, 2017. The increase to net product sales was attributable to an increase in price net of deductions.Cost of goods sold. Cost of goods sold increased by $2.7 million, or 15%, to $20.5 million for the year ended December 31, 2018 compared to $17.8million for the year ended December 31, 2017. Cost of goods sold includes third party manufacturing costs of product sold, third party royalty costs anddistribution and other costs. Third party royalty costs were 10% of net sales of HETLIOZ® in the U.S. and 9% of net sales of Fanapt®.In addition to third party royalty costs, HETLIOZ® and Fanapt® cost of goods sold as a percentage of revenue depends upon our cost to manufactureinventory at normalized production levels with our third party manufacturers. We expect that, in the future, total HETLIOZ® manufacturing costs included incost of goods sold will continue to be less than 2% of our net HETLIOZ® product sales. We expect that, in the future, total U.S. Fanapt® manufacturing costsincluded in cost of goods sold will continue to be less than 3% of our net U.S. Fanapt® product sales.Research and development expenses. Research and development expenses increased by $5.0 million, or 13%, to $43.6 million for the year endedDecember 31, 2018 compared to $38.5 million for the year ended December 31, 2017. The increase60Table of Contentswas primarily due to an increase in clinical trial expenses associated with the tradipitant gastroparesis and chronic pruritus in atopic dermatitis programs,preclinical expenses associated with the CFTR programs, as well as clinical manufacturing expenses for our Fanapt LAI program, partially offset by adecrease in expenses associated with the HETLIOZ® clinical programs and a $2.0 million expense accrued during the year ended December 31, 2017 for amilestone obligation payable to Eli Lilly and Company (Lilly) for tradipitant. The following table summarizes the costs of our product development initiatives for the year ended December 31, 2018 and 2017. Year Ended December 31,(in thousands)2018 2017Direct project costs (1) HETLIOZ®12,709 16,894Fanapt®3,438 2,179Tradipitant16,978 11,645VTR-2972,190 1,978CFTR3,870 1,949Other619 425 39,804 35,070Indirect project costs (1) Stock-based compensation1,290 1,152Other indirect overhead2,500 2,325 3,790 3,477Total research and development expense$43,594 $38,547 (1)We record direct costs, including personnel costs and related benefits, on a project-by-project basis. Many of our research and development costs arenot attributable to any individual project because we share resources across several development projects. We record indirect costs that support anumber of our research and development activities in the aggregate, including stock-based compensation.We expect to incur significant research and development expenses as we continue to develop our products. In addition, we expect to incur licensingcosts in the future that could be substantial, as we continue our efforts to expand our product pipeline.Selling, general and administrative expenses. Selling, general and administrative expenses decreased by $18.1 million, or 15%, to $105.8 millionfor the year ended December 31, 2018 compared to $123.8 million for the year ended December 31, 2017. The decrease was primarily the result of lowerspend on Non-24 direct to consumer advertising and sales force costs relating to HETLIOZ® and Fanapt® in the U.S.Intangible asset amortization. Intangible asset amortization was $1.5 million for the year ended December 31, 2018 compared to $1.8 million for theyear ended December 31, 2017.Other income. Other income was $3.6 million for the year ended December 31, 2018 compared to $1.5 million for the year ended December 31,2017. The increase was primarily the result of an increase in investment income due to an increase in our balance of marketable securities from the proceedsof the public offering of our common stock completed in March 2018 and a higher yield on investments.Provision for income taxes. The provision for income taxes was $0.1 million for each of the years ended December 31, 2018 and 2017. As a result ofthe tax valuation allowance against deferred tax assets in the U.S., there was no expense (benefit) for U.S. federal income taxes associated with the income(loss) before income taxes for the years ended December 31, 2018 and 2017. Taxes have been recorded related to certain U.S. state jurisdictions and non-U.S.income for the years ended December 31, 2018 and 2017. The effective tax rate for the year ended December 31, 2017 included our estimate of the effect of the Tax Cuts and Jobs Act (TCJA). The adjustmentthat was recorded results in no tax expense as it is fully offset by a change in our valuation61Table of Contentsallowance. In the fourth quarter of 2018 we completed our accounting of the income tax effects of the TCJA. No material measurement period adjustmentswere recorded in 2018 to adjust estimated effects of the TCJA that were recorded in 2017. Immaterial measurement period adjustments that were recordedresulted in no tax expense as they were fully offset by a change in our valuation allowance.Year ended December 31, 2017 compared to year ended December 31, 2016Revenues. Total revenues increased by $19.1 million, or 13%, to $165.1 million for the year ended December 31, 2017 compared to $146.0 millionfor the year ended December 31, 2016. During the years ended December 31, 2017 and 2016, revenues consisted of the following: Year Ended December 31,(in thousands)2017 2016 Net Change PercentHETLIOZ® product sales, net$89,978 $71,671 $18,307 26%Fanapt® product sales, net75,105 74,346 759 1% $165,083 $146,017 $19,066 13%HETLIOZ® product sales, net increased by $18.3 million, or 26%, to $90.0 million for the year ended December 31, 2017 compared to $71.7 millionfor the year ended December 31, 2016. The increase to net product sales was attributable to an increase in volume and, to a lesser extent, an increase to pricenet of deductions.Fanapt® product sales, net increased by $0.8 million, or 1%, to $75.1 million for the year ended December 31, 2017 compared to $74.3 million forthe year ended December 31, 2016. The increase to net product sales was attributable to an increase in price net of deductions and partially offset by adecrease in volume.Cost of goods sold. Cost of goods sold was $17.8 million for the year ended December 31, 2017 compared to $24.7 million for the year endedDecember 31, 2016. Cost of goods sold includes third party manufacturing costs of product sold, third party royalty costs and distribution and other costs.Third party royalty costs are 10% of net sales of HETLIOZ®. Third party royalty costs were 23% of net U.S. sales of Fanapt® through November 15, 2016 and9% thereafter. The decrease was primarily the result of the change in the royalty rate on Fanapt® sales partially offset by an increase in HETLIOZ® third partyroyalty costs due to increase in revenue.In addition to third party royalty costs, HETLIOZ® and Fanapt® cost of goods sold as a percentage of revenue depends upon our cost to manufactureinventory at normalized production levels with our third party manufacturers. We expect that, in the future, total HETLIOZ® manufacturing costs included incost of goods sold will continue to be less than 2% of our net HETLIOZ® product sales. We expect that, in the future, total U.S. Fanapt® manufacturing costsincluded in cost of goods sold will continue to be less than 4% of our net U.S. Fanapt® product sales.Research and development expenses. Research and development expenses were $38.5 million and $29.2 million for the years ended December 31,2017 and 2016, respectively. Expenses for tradipitant for the year ended December 31, 2017 include an accrued expense of $2.0 million for a milestoneobligation that is payable to Lilly upon enrollment of the first subject into a Phase III study for tradipitant. The likelihood of achieving this milestone wasdetermined to be probable during 2017. As a result, the future obligation of $2.0 million tied to such milestone was recorded as research and developmentexpense. Clinical trial expenses associated with the HETLIOZ® jet lag disorder program and the tradipitant gastroparesis program increased for the year endedDecember 31, 2017 compared to year ended December 31, 2016. In addition, during the year ended December 31, 2017, expenses include a $1.0 millioninitial license fee to develop and commercialize a portfolio of CFTR activators and inhibitors. These increases were partially offset by a decrease in indirectproject costs reflecting lower stock-based compensation expense.62Table of ContentsThe following table summarizes the costs of our product development initiatives for the year ended December 31, 2017 and 2016. Year Ended December 31,(in thousands)2017 2016Direct project costs (1) HETLIOZ®$16,894 $12,658Fanapt®2,179 2,598Tradipitant11,645 7,010VTR-2971,978 2,218CFTR1,949 —Other425 — 35,070 24,484Indirect project costs (1) Stock-based compensation1,152 2,087Other indirect overhead2,325 2,585 3,477 4,672Total research & development expense$38,547 $29,156 (1)We record direct costs, including personnel costs and related benefits, on a project-by-project basis. Many of our research and development costs arenot attributable to any individual project because we share resources across several development projects. We record indirect costs that support anumber of our research and development activities in the aggregate, including stock-based compensation expense.We expect to incur significant research and development expenses as we continue to develop our products. In addition, we expect to incur licensingcosts in the future that could be substantial, as we continue our efforts to expand our product pipeline.Selling, general and administrative expenses. Selling, general and administrative expenses increased by $24.0 million, or 24%, to $123.8 millionfor the year ended December 31, 2017 compared to $99.8 million for the year ended December 31, 2016. The increase was primarily the result of the Fanapt®sales force expansion, marketing efforts around Fanapt® in the U.S. and HETLIOZ® in the U.S. and Europe and, to a lesser extent, an increase in stock-basedcompensation expense, partially offset by a decrease in legal fees associated with ongoing patent litigation.Intangible asset amortization. Intangible asset amortization was $1.8 million for the year ended December 31, 2017 compared to $10.9 million forthe year ended December 31, 2016. Amortization of intangible assets relating to Fanapt® was completed in November 2016 and had amounted to$9.2 million for the year ended December 31, 2016. The useful life estimation for the Fanapt® intangible asset was based on the market participantmethodology prescribed by ASC 805, and therefore does not reflect the impact of additional Fanapt® patents solely owned by us with varying expirationdates, the latest of which is December 2031. We expect that annual amortization of capitalized intangible asset costs relating to HETLIOZ® will amount toapproximately $1.6 million in future years until the final expiration of the related product patents in 2034.Provision for income taxes. The provision for income taxes was $0.1 million for each of the years ended December 31, 2017 and 2016, respectively.The tax provision for each year is attributable to activities at our foreign subsidiaries and state income taxes. The tax benefit relating to the loss beforeincome taxes for the years ended December 31, 2017 and 2016 in the U.S. was fully offset by a tax valuation allowance resulting from our assessment that it ismore likely than not that our deferred tax assets will not be realized. The ultimate realization of deferred tax assets is dependent upon the generation of futuretaxable income during the period in which NOLs and credit carryforwards can be utilized.The effective tax rate for the year ended December 31, 2017 includes our estimate of the effect of the TCJA. The adjustment that was recorded resultsin no tax expense as it is fully offset by a change in our valuation allowance. Because of our valuation allowance in the U.S., ongoing tax effects of the TCJAare not expected to materially change our effective tax rate in future periods.63Table of ContentsLiquidity and Capital ResourcesAs of December 31, 2018, our total cash and cash equivalents and marketable securities were $257.4 million compared to $143.4 million atDecember 31, 2017. Our cash and cash equivalents are deposits in operating accounts and highly liquid investments with an original maturity of 90 days orless at date of purchase and consist of investments in money market funds with commercial banks and financial institutions, and commercial paper of high-quality corporate issuers. Our marketable securities consist of investments in government sponsored and corporate enterprises and commercial paper.Our liquidity resources as of December 31, 2018 and 2017 are summarized as follows: (in thousands)December 31, 2018 December 31, 2017Cash and cash equivalents$61,005 $33,627Marketable securities: U.S. Treasury and government agencies69,270 60,618Corporate debt105,910 49,168Asset-backed securities21,175 —Total marketable securities196,355 109,786Total cash, cash equivalents and marketable securities$257,360 $143,413As of December 31, 2018, we maintained all of our cash and cash equivalents in two financial institutions. Deposits held with these institutions mayexceed the amount of insurance provided on such deposits, but we do not anticipate any losses with respect to such deposits.We expect to incur substantial costs and expenses throughout 2019 and beyond in connection with our continued clinical development oftradipitant and our other products, U.S. commercial activities for HETLIOZ® and Fanapt®, the European commercial launch activities for HETLIOZ® andpayments due upon achievement of milestones under our license agreements. Additionally, we continue to pursue market approval of HETLIOZ® andFanapt® in other regions. The actual costs to advance tradipitant and our research and development projects and commercial activities for HETLIOZ® andFanapt® are difficult to estimate and may vary significantly. Management believes that our existing funds will be sufficient to meet our operating plans for atleast the next twelve months. Our future capital requirements and the adequacy of our available funds will depend on many factors, primarily including ourability to generate revenue, the scope and costs of our commercial, manufacturing and process development activities, the magnitude of our discovery,preclinical and clinical development programs, and potential costs to acquire or license the rights to additional products.We may need or desire to obtain additional capital to finance our operations through debt, equity or alternative financing arrangements. We mayalso seek capital through collaborations or partnerships with other companies. The issuance of debt could require us to grant liens on certain of our assets thatmay limit our flexibility and debt securities may be convertible into common stock. If we raise additional capital by issuing equity securities, the terms andprices for these financings may be much more favorable to the new investors than the terms obtained by our existing stockholders. These financings also maysignificantly dilute the ownership of our existing stockholders. If we are unable to obtain additional financing, we may be required to reduce the scope of ourfuture activities which could harm our business, financial condition and operating results. There can be no assurance that any additional financing requiredin the future will be available on acceptable terms, if at all.64Table of ContentsCash flowThe following table summarizes our net cash flows from operating, investing and financing activities for the years ended December 31, 2018, 2017and 2016: Year Ended December 31,(in thousands)2018 2017 2016Net cash provided by (used in): Operating activities: Net income (loss)$25,208 $(15,567) $(18,010)Non-cash charges12,568 13,610 21,015Net change in operating assets and liabilities(7,790) (26) (11,108)Operating activities29,986 (1,983) (8,103)Investing activities: Acquisition of intangible asset(25,000) — —Purchases of property and equipment(368) (1,664) (1,407)Net purchases of marketable securities(84,292) (8,567) (8,618)Investing activities(109,660) (10,231) (10,025)Financing activities: Net proceeds from offering of common stock100,870 — —Proceeds from exercise of employee stock options and other6,256 5,251 7,751Financing activities107,126 5,251 7,751Effect of exchange rate changes on cash and cash equivalents(38) 42 5Net increase (decrease) in cash and cash equivalents$27,414 $(6,921) $(10,372)Year ended December 31, 2018 compared to year ended December 31, 2017Net cash provided by operating activities was $30.0 million for the year ended December 31, 2018, an increase of $32.0 million compared to netcash used of $2.0 million for the year ended December 31, 2017. The increase reflects an increase of $40.8 million in net income, partially offset by adecrease of $7.8 million from the net change in operating assets and liabilities. The decrease of $7.8 million from the net change in operating assets andliabilities primarily relates to an increase in accounts receivable attributable to an increase in net product sales, partially offset by an increase in productrevenue allowances and the payment of a $2.0 million accrued milestone obligation during the year ended December 31, 2018.Year ended December 31, 2017 compared to year ended December 31, 2016Net cash used in operating activities was $2.0 million for the year ended December 31, 2017, a decrease of $6.1 million compared to net cash used of$8.1 million for the year ended December 31, 2016. The decrease reflects a decrease of $2.4 million in the net loss and a decrease of $11.1 million from thenet change in operating assets and liabilities, partially offset by a decrease of $7.4 million in non-cash charges resulting primarily from completion of theamortization of intangible assets related to Fanapt® in November 2016. The decrease of $11.1 million from the net change in operating assets and liabilitiesprimarily relates to a reduction in accrued government and other rebates, a decrease in accounts receivable attributable to the timing of shipments andpayments, and a decrease in prepaid expenses and other associated with a decrease in prepaid marketing expenses and prepaid royalties.Off-balance sheet arrangementsWe have no off-balance sheet arrangements, as defined in Item 303(a)(4) of the Securities and Exchange Commission’s Regulation S-K.65Table of ContentsContractual obligations and commitmentsThe following is a summary of our non-cancellable long-term contractual cash obligations as of December 31, 2018: Cash payments due by year(in thousands)Total 2019 2020 2021 2022 2023 ThereafterOperating leases (1)$22,757 $2,483 $2,495 $2,335 $2,355 $2,420 $10,669Milestone obligation (2) (3)200 200 — — — — —Purchase commitments (4)7,315 5,122 847 890 456 — — $30,272 $7,805 $3,342 $3,225 $2,811 $2,420 $10,669 (1)This table includes minimum annual future payments under operating leases and subleases for a total of 43,462 square feet of office space for ourheadquarters office at 2200 Pennsylvania Avenue, N.W. in Washington, D.C. that generally expire in 2028, an operating lease for 2,880 square feet ofoffice space for our European headquarters in London that has a noncancellable lease term ending in 2021, and 1,249 square feet of office space in Berlinunder a short-term operating lease.(2)This table does not include potential future milestone obligations under our license agreement with Lilly for the exclusive rights to develop andcommercialize tradipitant of $97.0 million, which consist of $2.0 million due upon the filing of the first marketing authorization for tradipitant in eitherthe U.S. or the E.U., $10.0 million and $5.0 million for the first approval of a marketing authorization for tradipitant in the U.S. and the E.U., respectively,and up to $80.0 million for future sales milestones.(3)This table does not include potential future milestone obligations under our license agreement with the University of California San Francisco for theexclusive rights to develop and commercialize a portfolio of CFTR activators and inhibitors under which we could be obligated to make potential futuremilestone payments of up to $45.2 million, which includes $12.2 million for pre-NDA approval milestones and $33.0 million for future regulatoryapproval and sales milestones. Included in the $12.2 million in pre-NDA approval milestones is a $350,000 milestone due upon the conclusion of aPhase I study for each licensed product but not to exceed $1.1 million in total for the CFTR portfolio.(4)Purchase commitments include noncancellable purchase commitments for agreements longer than one year and primarily relate to commitments foradvertising and data services. This table does not include various other long-term agreements entered into for services with other third party vendors dueto the cancelable nature of the services. Additionally, this table does not include rebates, chargebacks or discounts recorded as liabilities at the time thatproduct sales are recognized as revenue.ITEM 7A.QUALITATIVE AND QUANTITATIVE DISCLOSURES ABOUT MARKET RISK Interest rate risksOur exposure to market risk is currently confined to our cash and cash equivalents, marketable securities and restricted cash. We currently do nothedge interest rate exposure. We have not used derivative financial instruments for speculation or trading purposes. Because of the short-term maturities ofour cash and cash equivalents and marketable securities, we do not believe that an increase in market rates would have any significant impact on the realizedvalue of our investments. Concentrations of credit riskWe deposit our cash with financial institutions that we consider to be of high credit quality and purchase marketable securities which are generallyinvestment grade, liquid, short-term fixed income securities and money-market instruments denominated in U.S. dollars. Our marketable securities consist ofcommercial paper, corporate notes, asset-backed securities and U.S. government agency notes.Revenues and accounts receivable are concentrated with specialty pharmacies and wholesalers. There were 5 major customers that each accountedfor more than 10% of total revenues and, as a group, represented 92% of total revenues for the year ended December 31, 2018. There were 5 major customersthat each accounted for more than 10% of accounts receivable and, as a group, represented 94% of total accounts receivable at December 31, 2018. Wemitigate our credit risk relating to accounts receivable from customers by performing ongoing credit evaluations. 66Table of ContentsForeign currency riskWe are exposed to risks related to changes in foreign currency exchange rates relating to our foreign operations. The functional currency of ourinternational subsidiaries is the local currency. We are exposed to foreign currency risk to the extent that we enter into transactions denominated incurrencies other than our subsidiaries’ respective functional currencies. We are also exposed to unfavorable fluctuations of the U.S. dollar, which is ourreporting currency, against the currencies of our operating subsidiaries when their respective financial statements are translated into U.S. dollars for inclusionin our consolidated financial statements. We do not currently hedge our foreign currency exchange rate risk. Foreign currency has not had a material impacton our results of operations.Effects of inflationInflation has not had a material impact on our results of operations. ITEM 8.FINANCIAL STATEMENTS AND SUPPLEMENTARY DATAThe consolidated financial statements and related financial statement schedules required to be filed are listed in the Index to Consolidated FinancialStatements and are incorporated in Item 15 of Part IV of this annual report on Form 10-K. ITEM 9.CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURENone. ITEM 9A.CONTROLS AND PROCEDURES Conclusion Regarding the Effectiveness of Disclosure Controls and ProceduresUnder the supervision and with the participation of our management, including the Chief Executive Officer and Chief Financial Officer, weevaluated the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under theSecurities and Exchange Act of 1934 (Exchange Act)) as of December 31, 2018. Based upon that evaluation, our Chief Executive Officer and Chief FinancialOfficer concluded that our disclosure controls and procedures are effective as of December 31, 2018, the end of the period covered by this annual report onForm 10-K, to ensure that the information required to be disclosed by us in the reports that we file or submit under the Exchange Act is recorded, processed,summarized and reported within the time periods specified in the SEC’s rules and forms, and that such information is accumulated and communicated to ourmanagement, including our Chief Executive Officer and Chief Financial Officer, as appropriate to allow timely decisions regarding required disclosures.Management’s Report on Internal Control over Financial ReportingOur management is responsible for establishing and maintaining an adequate system of internal control over financial reporting, as defined in theExchange Act Rule 13a-15(f). Management conducted an assessment of our internal control over financial reporting based on the original frameworkestablished in 2013 by the Committee of Sponsoring Organizations of the Treadway Commission in Internal Control — Integrated Framework. Based on theassessment, management concluded that, as of December 31, 2018, our internal control over financial reporting was effective. The effectiveness of ourinternal control over financial reporting as of December 31, 2018 has been audited by PricewaterhouseCoopers LLP, an independent registered publicaccounting firm, as stated in their report included in this annual report on Form 10-K.Changes in Internal Control over Financial ReportingThere has been no change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act)during the fourth quarter of 2018 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting. 67Table of ContentsITEM 9B.OTHER INFORMATION None. PART IIIITEM 10.DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE Information required under this item will be contained in our Proxy Statement for the 2019 Annual Meeting of Stockholders to be filed with the SECwithin 120 days after the end of the fiscal year ended December 31, 2018, under the captions “Election of Directors,” “Executive Officers,” “CorporateGovernance,” and “Section 16(a) Beneficial Ownership Reporting Compliance” and is incorporated herein by reference pursuant to General Instruction G(3)to Form 10-K. ITEM 11.EXECUTIVE COMPENSATION Information required under this item will be contained in our Proxy Statement for the 2019 Annual Meeting of Stockholders to be filed with the SECwithin 120 days after the end of the fiscal year ended December 31, 2018, under the captions “Corporate Governance” and “Executive Compensation,” and isincorporated herein by reference pursuant to General Instruction G(3) to Form 10-K, except that information required by Item 407(e)(5) of Regulation S-Kwill be deemed furnished in this Form 10-K and will not be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, orthe Securities Exchange Act of 1934, as amended, except to the extent that we specifically incorporate it by reference into such filing. ITEM 12.SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDERMATTERS Information required under this item will be contained in our Proxy Statement for the 2019 Annual Meeting of Stockholders to be filed with the SECwithin 120 days after the end of the fiscal year ended December 31, 2018, under the captions “Equity Compensation Plan Information” and “SecurityOwnership of Certain Beneficial Owners and Management” and is incorporated herein by reference pursuant to General Instruction G(3) to Form 10-K.ITEM 13.CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE Information required under this item will be contained in our Proxy Statement for the 2019 Annual Meeting of Stockholders to be filed with the SECwithin 120 days after the end of the fiscal year ended December 31, 2018, under the caption “Corporate Governance” and is incorporated herein by referencepursuant to General Instruction G(3) to Form 10-K.ITEM 14.PRINCIPAL ACCOUNTANT FEES AND SERVICES Information required under this item will be contained in our Proxy Statement for the 2019 Annual Meeting of Stockholders to be filed with the SECwithin 120 days after the end of the fiscal year ended December 31, 2018, under the caption “Ratification of Selection of Independent Registered PublicAccounting Firm” and is incorporated herein by reference pursuant to General Instruction G (3) to Form 10-K.PART IV 68Table of ContentsITEM 15.EXHIBITS AND FINANCIAL STATEMENTS SCHEDULES The consolidated financial statements filed as part of this annual report on Form 10-K are listed in the Index to Consolidated Financial Statements.Certain schedules are omitted because they are not applicable, or not required, or because the required information is included in the consolidated financialstatements or notes thereto. The Exhibits are listed in the Exhibit Index.69Table of ContentsSignaturesPursuant to the requirements of Section 13 and 15(d) of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this annualreport on Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized. Vanda Pharmaceuticals Inc. February 19, 2019 By: /s/ Mihael H. Polymeropoulos, M.D. Mihael H. Polymeropoulos, M.D. President and Chief Executive OfficerPursuant to the requirements of the Securities Act of 1934, this annual report on Form 10-K has been signed below by the following persons onbehalf of the registrant and in the capacities and on the dates indicated.Name Title Date /s/ Mihael H. Polymeropoulos, M.D. President and Chief Executive Officer and Director(principal executive officer) February 19, 2019Mihael H. Polymeropoulos, M.D. /s/ James P. Kelly Executive Vice President, Chief Financial Officerand Treasurer (principal financialofficer and principal accounting officer) February 19, 2019James P. Kelly /s/ H. Thomas Watkins Chairman of the Board andDirector February 19, 2019H. Thomas Watkins /s/ Michael Cola Director February 19, 2019Michael Cola /s/ Richard W. Dugan Director February 19, 2019Richard W. Dugan /s/ Vincent J. Milano Director February 19, 2019Vincent J. Milano 70Table of ContentsVanda Pharmaceuticals Inc.Index to Consolidated Financial Statements PageReport of Independent Registered Public Accounting Firm72Consolidated Balance Sheets at December 31, 2018 and 201774Consolidated Statements of Operations for the years ended December 31, 2018, 2017 and 201675Consolidated Statements of Comprehensive Income (Loss) for the years ended December 31, 2018, 2017 and 201676Consolidated Statements of Changes in Stockholders’ Equity for the years ended December 31, 2018, 2017 and 201677Consolidated Statements of Cash Flows for the years ended December 31, 2018, 2017 and 201678Notes to the Consolidated Financial Statements7971Table of ContentsReport of Independent Registered Public Accounting FirmTo the Board of Directors and Stockholders of Vanda Pharmaceuticals Inc.Opinions on the Financial Statements and Internal Control over Financial ReportingWe have audited the consolidated financial statements, including the related notes, of Vanda Pharmaceuticals Inc. and its subsidiaries (the “Company”) aslisted in the accompanying index (collectively referred to as the “consolidated financial statements”). We also have audited the Company's internal controlover financial reporting as of December 31, 2018, based on criteria established in Internal Control - Integrated Framework (2013) issued by the Committeeof Sponsoring Organizations of the Treadway Commission (COSO).In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of the Company as ofDecember 31, 2018 and 2017, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2018 inconformity with accounting principles generally accepted in the United States of America. Also in our opinion, the Company maintained, in all materialrespects, effective internal control over financial reporting as of December 31, 2018, based on criteria established in Internal Control - Integrated Framework(2013) issued by the COSO.Basis for OpinionsThe Company's management is responsible for these consolidated financial statements, for maintaining effective internal control over financial reporting, andfor its assessment of the effectiveness of internal control over financial reporting, included in Management's Report on Internal Control over FinancialReporting appearing under Item 9A. Our responsibility is to express opinions on the Company’s consolidated financial statements and on the Company'sinternal control over financial reporting based on our audits. We are a public accounting firm registered with the Public Company Accounting OversightBoard (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and theapplicable rules and regulations of the Securities and Exchange Commission and the PCAOB.We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonableassurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud, and whether effective internalcontrol over financial reporting was maintained in all material respects.Our audits of the consolidated financial statements included performing procedures to assess the risks of material misstatement of the consolidated financialstatements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis,evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles usedand significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. Our audit of internalcontrol over financial reporting included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weaknessexists, and testing and evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audits also included performingsuch other procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for our opinions.Definition and Limitations of Internal Control over Financial ReportingA company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reportingand the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal controlover financial reporting includes those policies and procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairlyreflect the transactions and dispositions of the assets of the company; (ii) provide reasonable assurance that transactions are recorded as necessary to permitpreparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are beingmade only in accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding prevention ortimely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.72Table of ContentsBecause of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation ofeffectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliancewith the policies or procedures may deteriorate./s/ PricewaterhouseCoopers LLPBaltimore, MDFebruary 19, 2019We have served as the Company’s auditor since 2003.73Table of ContentsVANDA PHARMACEUTICALS INC.CONSOLIDATED BALANCE SHEETS(in thousands, except for share and per share amounts)December 31, 2018 December 31, 2017ASSETS Current assets: Cash and cash equivalents$61,005 $33,627Marketable securities196,355 109,786Accounts receivable, net28,780 17,601Inventory994 840Prepaid expenses and other current assets11,998 8,003Total current assets299,132 169,857Property and equipment, net4,417 5,306Intangible assets, net24,542 26,069Non-current inventory and other4,039 4,193Total assets$332,130 $205,425LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable and accrued liabilities$21,584 $20,335Product revenue allowances31,231 23,028Milestone obligations under license agreements200 27,000Total current liabilities53,015 70,363Other non-current liabilities3,693 3,675Total liabilities56,708 74,038Commitments and contingencies (Notes 9 and 16) Stockholders’ equity: Preferred stock, $0.001 par value; 20,000,000 shares authorized, and no shares issued or outstanding— —Common stock, $0.001 par value; 150,000,000 shares authorized; 52,477,593 and 44,938,133 sharesissued and outstanding at December 31, 2018 and 2017, respectively52 45Additional paid-in capital611,587 492,802Accumulated other comprehensive income (loss)1 (34)Accumulated deficit(336,218) (361,426)Total stockholders’ equity275,422 131,387Total liabilities and stockholders’ equity$332,130 $205,425The accompanying notes are an integral part of these consolidated financial statements.74Table of ContentsVANDA PHARMACEUTICALS INC.CONSOLIDATED STATEMENTS OF OPERATIONS Year Ended December 31,(in thousands, except for share and per share amounts)2018 2017 2016Revenues: Net product sales$193,118 $165,083 $146,017Total revenues193,118 165,083 146,017Operating expenses: Cost of goods sold excluding amortization20,508 17,848 24,712Research and development43,594 38,547 29,156Selling, general and administrative105,751 123,841 99,787Intangible asset amortization1,527 1,750 10,933Total operating expenses171,380 181,986 164,588Income (loss) from operations21,738 (16,903) (18,571)Other income3,608 1,472 665Income (loss) before income taxes25,346 (15,431) (17,906)Provision for income taxes138 136 104Net income (loss)$25,208$(15,567)$(18,010)Net income (loss) per share: Basic$0.50 $(0.35) $(0.41)Diluted$0.48 $(0.35) $(0.41)Weighted average shares outstanding: Basic50,859,947 44,735,146 43,449,441Diluted53,045,257 44,735,146 43,449,441The accompanying notes are an integral part of these consolidated financial statements.75Table of ContentsVANDA PHARMACEUTICALS INC.CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) Year Ended December 31,(in thousands)2018 2017 2016Net income (loss)$25,208 $(15,567) $(18,010)Other comprehensive income (loss): Net foreign currency translation gain (loss)(22) 30 (1)Change in net unrealized gain (loss) on marketable securities57 (122) 20Tax provision on other comprehensive income— — —Other comprehensive income (loss), net of tax35 (92) 19Comprehensive income (loss)$25,243$(15,659)$(17,991)The accompanying notes are an integral part of these consolidated financial statements.76Table of ContentsVANDA PHARMACEUTICALS INC.CONSOLIDATED STATEMENTS OF CHANGES IN STOCKHOLDERS’ EQUITY Common Stock Additional Paid-in Capital Other Comprehensive Income (Loss) Accumulated Deficit Total(in thousands, except for share amounts)Shares Par Value Balances at December 31, 201542,815,291 $43 $460,794 $39 $(327,849) $133,027Issuance of common stock from theexercise of stock options andsettlement of restricted stock units1,185,323 1 7,750 — — 7,751Stock-based compensation expense— — 8,543 — — 8,543Net loss— — — — (18,010) (18,010)Other comprehensive income, net of tax— — — 19 — 19Balances at December 31, 201644,000,61444477,08758(345,859)131,330Issuance of common stock from theexercise of stock options andsettlement of restricted stock units937,519 1 5,250 — — 5,251Stock-based compensation expense— — 10,465 — — 10,465Net loss— — — — (15,567) (15,567)Other comprehensive loss, net of tax— — — (92) — (92)Balances at December 31, 201744,938,13345492,802(34)(361,426)131,387Net proceeds from public offering ofcommon stock6,325,000 6 100,864 — — 100,870Issuance of common stock from theexercise of stock options andsettlement of restricted stock units1,214,460 1 6,255 — — 6,256Stock-based compensation expense— — 11,666 — — 11,666Net income— — — — 25,208 25,208Other comprehensive income, net of tax— — — 35 — 35Balances at December 31, 201852,477,59352611,5871(336,218)275,422The accompanying notes are an integral part of these consolidated financial statements.77Table of ContentsVANDA PHARMACEUTICALS INC.CONSOLIDATED STATEMENTS OF CASH FLOWS Year Ended December 31,(in thousands)2018 2017 2016Cash flows from operating activities Net income (loss)$25,208 $(15,567) $(18,010)Adjustments to reconcile net income (loss) to net cash provided by (used in) operatingactivities: Depreciation of property and equipment1,429 1,234 935Stock-based compensation11,666 10,465 8,543Amortization of premiums (discounts) on marketable securities(2,221) (426) 62Intangible asset amortization1,527 1,750 10,933Other non-cash adjustments, net167 587 542Changes in operating assets and liabilities: Accounts receivable(11,207) 2,525 (4,298)Prepaid expenses and other assets(4,258) 3,652 (6,159)Inventory70 (1,060) 200Accounts payable and other liabilities(618) 5,953 575Product revenue allowances8,223 (11,096) (1,426)Net cash provided by (used in) operating activities29,986 (1,983) (8,103)Cash flows from investing activities Acquisition of intangible asset(25,000) — —Purchases of property and equipment(368) (1,664) (1,407)Purchases of marketable securities(282,395) (148,135) (165,405)Maturities of marketable securities198,103 139,568 156,787Net cash used in investing activities(109,660)(10,231)(10,025)Cash flows from financing activities Net proceeds from offering of common stock100,870 — —Proceeds from exercise of employee stock options6,256 5,251 7,751Net cash provided by financing activities107,1265,2517,751Effect of exchange rate changes on cash, cash equivalents and restricted cash(38) 42 5Net increase (decrease) in cash, cash equivalents and restricted cash27,414 (6,921) (10,372)Cash, cash equivalents and restricted cash Beginning of year34,335 41,256 51,628End of year$61,749$34,335$41,256The accompanying notes are an integral part of these consolidated financial statements.78Table of ContentsVANDA PHARMACEUTICALS INC.NOTES TO CONSOLIDATED FINANCIAL STATEMENTS 1. Business Organization and PresentationBusiness organizationVanda Pharmaceuticals Inc. (the Company) is a global biopharmaceutical company focused on the development and commercialization ofinnovative therapies to address high unmet medical needs and improve the lives of patients. The Company commenced its operations in 2003 and operates inone reporting segment. The Company’s portfolio includes the following products: •HETLIOZ® (tasimelteon), a product for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24), was approved by the U.S. Food and DrugAdministration (FDA) in January 2014 and launched commercially in the U.S. in April 2014. In July 2015, the European Commission (EC)granted centralized marketing authorization with unified labeling for HETLIOZ® for the treatment of Non-24 in totally blind adults. HETLIOZ®was commercially launched in Germany in August 2016. HETLIOZ® has potential utility in a number of other circadian rhythm disorders and ispresently in clinical development for the treatment of jet lag disorder, Smith-Magenis Syndrome (SMS) and Pediatric Non-24. An assessment ofnew HETLIOZ® clinical opportunities including the treatment of delayed sleep phase disorder and for sleep disorders in patients withneurodevelopmental disorders is ongoing. •Fanapt® (iloperidone), a product for the treatment of schizophrenia, the oral formulation of which was approved by the FDA in May 2009 andlaunched commercially in the U.S. by Novartis Pharma AG (Novartis) in January 2010. Novartis transferred all the U.S. and Canadiancommercial rights to the Fanapt® franchise to the Company on December 31, 2014. Additionally, the Company’s distribution partners launchedFanapt® in Israel in 2014. Fanapt® has potential utility in a number of other disorders. Initial clinical work studying a long acting injectable(LAI) formulation of Fanapt® began in 2018. An assessment of new Fanapt® clinical opportunities including the treatment of bipolar depressionis ongoing. •Tradipitant (VLY-686), a small molecule neurokinin-1 receptor (NK-1R) antagonist, which is presently in clinical development for the treatmentof chronic pruritus in atopic dermatitis and the treatment of gastroparesis. An assessment of new tradipitant clinical opportunities including thetreatment of motion sickness is ongoing. •VTR-297, a small molecule histone deacetylase (HDAC) inhibitor presently in clinical development for the treatment of hematologicmalignancies. •Portfolio of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activators and inhibitors. An early stage CFTR activator program isplanned for the treatment of dry eye and ocular inflammation. In addition, an early stage CFTR inhibitor program is planned for the treatment ofsecretory diarrhea disorders, including cholera. •VQW-765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist.Basis of presentationThe accompanying consolidated financial statements includes the accounts of Vanda Pharmaceuticals Inc. and its wholly-owned subsidiaries andhave been prepared in accordance with accounting principles generally accepted in the United States of America (U.S.). All intercompany accounts andtransactions have been eliminated in consolidation.2. Summary of Significant Accounting PoliciesUse of EstimatesThe preparation of financial statements in conformity with accounting principles generally accepted in the United States of America requiresmanagement to make estimates that affect the reported amounts of assets and liabilities at the date of the financial statements, disclosure of contingent assetsand liabilities, and the reported amounts of revenue and expenses during the reporting period. Management continually re-evaluates its estimates, judgmentsand assumptions, and management’s evaluation could change. Actual results could differ from those estimates.79Table of ContentsCash and Cash EquivalentsFor purposes of the consolidated balance sheets and consolidated statements of cash flows, cash equivalents represent highly-liquid investmentswith a maturity date of three months or less at the date of purchase. Cash and cash equivalents includes investments in money market funds with commercialbanks and financial institutions, and commercial paper of high-quality corporate issuers.Marketable SecuritiesThe Company classifies all of its marketable securities as available-for-sale securities. The Company’s investment policy requires the selection ofhigh-quality issuers, with bond ratings of AAA to A1+/P1. Available-for-sale securities are carried at fair market value, with unrealized gains and lossesreported as a component of stockholders’ equity in accumulated other comprehensive income (loss). At each balance sheet date, the Company assessesavailable-for-sale securities in an unrealized loss position to determine whether the unrealized loss is other-than-temporary. If declines in the value ofavailable for-sale securities are determined to be other-than-temporary, a loss is recorded in earnings in the current period. Interest and dividend income isrecorded when earned and included in interest income. Premiums and discounts on marketable securities are amortized and accreted, respectively, to maturityand included in interest income. The Company uses the specific identification method in computing realized gains and losses on the sale of investments,which would be included in the consolidated statements of operations when generated. Marketable securities with a maturity of more than one year as of thebalance sheet date and which the Company does not intend to sell within the next twelve months are classified as non-current. All other marketable securitiesare classified as current.InventoryInventory, which is recorded at the lower of cost or net realizable value, includes the cost of third-party manufacturing and other direct and indirectcosts and is valued using the first-in, first-out method. The Company capitalizes inventory costs associated with its products upon regulatory approval when,based on management’s judgment, future commercialization is considered probable and the future economic benefit is expected to be realized; otherwise,such costs are expensed as research and development. Inventory not expected to be sold within 12 months following the balance sheet date are classified asnon-current.Intangible AssetsCosts incurred for products not yet approved by the FDA and for which no alternative future use exists are recorded as expense. Obligations formilestone payments to other pharmaceutical companies that may result in a capitalized intangible asset are recognized when it is deemed probable that themilestone event will occur. In the event a product has been approved by the FDA or an alternative future use exists for a product, patent and license costs arecapitalized and amortized on a straight-line basis over the estimated useful economic life of the of the related product patents. For intangible assets related toHETLIOZ®, the estimated useful life is the estimated economic useful life of the related product patents, the latest of which expires in February 2035.Intangible assets related Fanapt® have been fully amortized on a straight-line basis to November 2016. The useful life estimate for Fanapt® was based on themarket participant methodology prescribed by ASC 805, and therefore does not reflect the impact of additional Fanapt® patents solely owned by theCompany with varying expiration dates, the latest of which is December 2031.Property and EquipmentProperty and equipment are stated at cost less accumulated depreciation. The costs of leasehold improvements funded by or reimbursed by the lessorare capitalized and amortized as leasehold improvements along with a corresponding deferred rent liability. Depreciation of most property and equipment isprovided on a straight-line basis over the estimated useful lives of the assets. Leasehold improvements are amortized using a straight-line basis over the lesserof the estimated useful lives of the assets or the terms of the related leases. The costs of additions and improvements are capitalized, and repairs andmaintenance costs are charged to operations in the period incurred. Upon retirement or disposition of property and equipment, the cost and accumulateddepreciation are removed from the accounts and any resulting gain or loss is reflected in the statement of operations for that period.Accounts Payable and Accrued LiabilitiesThe Company’s management is required to estimate accrued liabilities as part of the process of preparing financial statements. The estimation ofaccrued liabilities involves identifying services that have been performed on the Company’s80Table of Contentsbehalf, and then estimating the level of service performed and the associated cost incurred for such services as of each balance sheet date in the financialstatements. Accrued liabilities include research and development expenses, such as accrued costs under contracts with clinical monitors, data managementorganizations and investigators in conjunction with clinical trials, fees to contract manufacturers in conjunction with the production of clinical materials,consulting and professional fees, such as lawyers and fees for marketing and other commercialization activities, accrued compensation and employeebenefits, such as accrued bonus, royalties payable under licensing agreements, and other accrued fees. Pursuant to management’s assessment of the servicesthat have been performed on clinical trials and other contracts, the Company recognizes these expenses as the services are provided. Such managementassessments include, but are not limited to: (i) an evaluation by the project manager of the work that has been completed during the period, (ii) measurementof progress prepared internally and/or provided by the third-party service provider, (iii) analyses of data that justify the progress, and (iv) management’sjudgment. In the event that the Company does not identify certain costs that have begun to be incurred or the Company under- or over-estimates the level ofservices performed or the costs of such services, the Company’s reported expenses for such period would be too low or too high.Revenue RecognitionIn accordance with Accounting Standards Codification (ASC) Subtopic 606 Revenue from Contracts with Customers (ASC 606), which theCompany adopted January 1, 2018, the Company accounts for a contract when it has approval and commitment from both parties, the rights of the parties areidentified, payment terms are identified, the contract has commercial substance and collectability of consideration is probable. The Company recognizesrevenue when control of the product is transferred to the customer in an amount that reflects the consideration the Company expects to be entitled to inexchange for those product sales, which is typically once the product physically arrives at the customer. Sales taxes, value add taxes, and usage-based taxesare excluded from revenues.The Company’s net product sales consist of sales of HETLIOZ® and Fanapt®. Net sales by product for the years ended December 31, 2018, 2017 and2016 were as follows: Year Ended December 31,(in thousands)2018 2017 2016HETLIOZ® product sales, net$115,835 $89,978 $71,671Fanapt® product sales, net77,283 75,105 74,346 $193,118$165,083$146,017Major CustomersHETLIOZ® is only available in the U.S. for distribution through a limited number of specialty pharmacies, and is not available in retail pharmacies.Specialty pharmacy customers include Diplomat Pharmacy, Inc., Accredo (a subsidiary of Express Scripts) and Walgreens Company. Fanapt® is available inthe U.S. for distribution through a limited number of wholesalers and is available in retail pharmacies. Wholesaler customers include Cardinal Health, Inc.,AmerisourceBergen Drug Corporation, and McKesson Corporation. The Company invoices and records revenue when its customers, specialty pharmaciesand wholesalers, receive product from the third-party logistics warehouse which is the point at which control is transferred to the customer. Revenues andaccounts receivable are concentrated with these customers. The following table presents each major customer that represented more than 10% of totalrevenues for the years ended December 31, 2018, 2017 and 2016: Year Ended December 31,Percent of Net Product Sales2018 2017 2016Distributor A37% 32% 23%Distributor B17% 10% 1%Distributor C14% 15% 16%Distributor D12% 12% 15%Distributor E12% 15% 16%Distributor F5% 11% 16%81Table of ContentsThe following table presents each major customer that represented more than 10% of accounts receivable, net, as of December 31, 2018 and 2017: December 31,Percent of Accounts Receivable, Net2018 2017Distributor A30% 28%Distributor B15% 9%Distributor C20% 18%Distributor D16% 21%Distributor E13% 10%Reserves for Variable ConsiderationThe transaction price is determined based upon the consideration to which the Company will be entitled in exchange for transferring product to thecustomer. The Company’s product sales are recorded net of applicable discounts, rebates, chargebacks, service fees, co-pay assistance and product returns thatare applicable for various government and commercial payors. The Company estimates the amount of variable consideration that should be included in thetransaction price utilizing the most likely amount method and updates its estimate at each reporting date. Variable consideration is included in thetransaction price if, in the Company’s judgment, it is probable that a significant future reversal of cumulative revenue under the contract will not occur.Reserves for variable consideration for rebates, chargebacks and co-pay assistance are based upon the insurance benefits of the end customer, which areestimated using historical activity and, where available, actual and pending prescriptions for which the Company has validated the insurancebenefits. Reserves for variable consideration are classified as product revenue allowances on the consolidated balance sheets, with the exception of prompt-pay discounts which are classified as reductions of accounts receivable. The reserve for product returns for which the product may not be returned for a periodof greater than one year from the balance sheet date is included as a component of other non-current liabilities in the consolidated balance sheets.Uncertainties related to variable consideration are generally resolved in the quarter subsequent to period end, with the exception of product returns which areresolved during the product expiry period specified in the customer contract. The Company currently records sales allowances for the following:Prompt-pay: Specialty pharmacies and wholesalers are offered discounts for prompt payment. The Company expects that the specialty pharmaciesand wholesalers will earn prompt payment discounts and, therefore, deducts the full amount of these discounts from total product sales whenrevenues are recognized.Rebates: Allowances for rebates include mandated and supplemental discounts under the Medicaid Drug Rebate Program as well as contractedrebate programs with other payors. Rebate amounts owed after the final dispensing of the product to a benefit plan participant are based uponcontractual agreements or legal requirements with public sector benefit providers, such as Medicaid. The allowance for rebates is based on statutoryor contracted discount rates and expected patient utilization.Chargebacks: Chargebacks are discounts that occur when contracted indirect customers purchase directly from specialty pharmacies andwholesalers. Contracted indirect customers, which currently consist primarily of Public Health Service institutions, non-profit clinics, and Federalgovernment entities purchasing via the Federal Supply Schedule, generally purchase the product at a discounted price. The specialty pharmacy orwholesaler, in turn, charges back the difference between the price initially paid by the specialty pharmacy or wholesaler and the discounted pricepaid to the specialty pharmacy or wholesaler by the contracted customer.Medicare Part D Coverage Gap: Medicare Part D prescription drug benefit mandates manufacturers to fund approximately 50% of the MedicarePart D insurance coverage gap for prescription drugs sold to eligible patients through 2018. Public Law No. 115-123, also known as the BipartisanBudget Act of 2018 enacted on February 9, 2018 increased the manufacturer discount from 50% to 70% effective in 2019 for applicable drugs.Vanda accounts for the Medicare Part D coverage gap using a point of sale model. Estimates for expected Medicare Part D coverage gap are based inpart on historical activity and, where available, actual and pending prescriptions for which the Company has validated the insurance benefits.Service Fees: The Company receives sales order management, data and distribution services from certain customers. These fees are based oncontracted terms and are known amounts. The Company accrues service fees at the time of revenue recognition, resulting in a reduction of productsales and the recognition of an accrued liability, unless it is a payment for a distinct good or service from the customer in which case the fair value ofthose distinct goods or services are recorded as selling, general and administrative expense.82Table of ContentsCo-payment Assistance: Patients who have commercial insurance and meet certain eligibility requirements may receive co-payment assistance. Co-pay assistance utilization is based on information provided by the Company’s third-party administrator.Product Returns: Consistent with industry practice, the Company generally offers direct customers a limited right to return as defined within theCompany’s returns policy. The Company considers several factors in the estimation process, including historical return activity, expiration dates ofproduct shipped to specialty pharmacies and wholesalers, inventory levels within the distribution channel, product shelf life, prescription trends andother relevant factors. The Company does not expect returned goods to be resalable. There was no right of return asset as of December 31, 2018 or2017. The following table summarizes activity for product returns as of and for the years ended December 31, 2018, 2017 and 2016: (in thousands)Reserve for ProductReturnsBalances at December 31, 2015$1,059Additions2,507Credits/payments(486)Balances at December 31, 20163,080Additions5,978Credits/payments(4,939)Balances at December 31, 20174,119Additions2,684Credits/payments(1,616)Balances at December 31, 2018$5,187Cost of Goods SoldCost of goods sold includes royalties payable, the cost of inventory sold, manufacturing and supply chain costs and product shipping and handlingcosts related to sales of HETLIOZ® and Fanapt® to the Company’s distribution partners.Research and Development ExpensesResearch and development expenses consist primarily of fees for services provided by third parties in connection with the clinical trials, costs ofcontract manufacturing services, milestone payments, costs of materials used in clinical trials and research and development, costs for regulatory consultantsand filings, depreciation of capital resources used to develop products, related facilities costs, and salaries, other employee-related costs and stock-basedcompensation for research and development personnel. The Company expenses research and development costs as they are incurred for products in thedevelopment stage, including manufacturing costs and milestone payments made under license agreements prior to FDA approval. Upon and subsequent toFDA approval, manufacturing and milestone payments related to license agreements are capitalized. Milestone payments are accrued when it is deemedprobable that the milestone event will be achieved. Costs related to the acquisition of intellectual property are expensed as incurred if the underlyingtechnology is developed in connection with the Company’s research and development efforts and has no alternative future use.Selling, General and Administrative ExpensesSelling, general and administrative expenses consist of salaries, stock-based compensation, facilities and third party expenses. Selling, general andadministrative expenses are associated with the activities of the executive, finance, accounting, information technology, business development, commercialsupport, trade and distribution, sales, marketing, legal, medical affairs and human resource functions. Additionally, selling, general and administrativeexpenses included an estimate for the annual Patient Protection and Affordable Care fee.Stock-Based CompensationCompensation costs for all stock-based awards to employees and directors are measured based on the grant date fair value of those awards andrecognized over the period during which the employee or director is required to perform service in exchange for the award. The Company recognizes theexpense over the award’s vesting period. The fair value of stock options83Table of Contentsgranted and restricted stock units (RSUs) awarded are amortized using the straight-line method. As stock-based compensation expense recognized in theconsolidated statements of operations is based on awards ultimately expected to vest, it has been reduced for estimated forfeitures. Forfeitures are estimated atthe time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.Advertising ExpenseThe Company expenses the costs of advertising, including branded promotional expenses, as incurred. Branded advertising expenses, recorded inselling, general and administrative expenses, were $0.9 million, $1.3 million and $1.4 million for the years ended December 31, 2018, 2017 and 2016,respectively.Foreign CurrencyThe reporting currency of the Company is the U.S. dollar. The functional currency of the Company’s international subsidiaries is the local currency.Assets and liabilities denominated in foreign currencies, including intercompany balances for which settlement is anticipated in the foreseeable future, aretranslated at exchange rates in effect at the balance sheet date. Foreign currency equity balances are translated at historical rates. Revenues and expensesdenominated in foreign currencies are translated at average exchange rates for the respective periods. Foreign currency translation adjustments are recorded inaccumulated other comprehensive income (loss).Transactions denominated in currencies other than subsidiaries’ functional currencies are recorded based on exchange rates at the time suchtransactions arise. Changes in exchange rates with respect to amounts recorded in the consolidated balance sheets related to these items will result inunrealized foreign currency transaction gains and losses based upon period-end exchange rates. The Company also records realized foreign currencytransaction gains and losses upon settlement of the transactions. Foreign currency transaction gains and losses are included in other income and amounted toloss of $0.5 million, income of $0.1 million, and loss of $0.2 million for the years ended December 31, 2018, 2017 and 2016, respectively.Income TaxesThe Company accounts for income taxes using the asset and liability method. Under the asset and liability method, current income tax expense orbenefit is the amount of income taxes expected to be payable or refundable for the current year. A deferred income tax asset or liability is recognized forfuture tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their respective taxbases and tax credits and loss carryforwards. Deferred tax assets are reduced by a valuation allowance when, in the opinion of management, it is more likelythan not that some portion or all of the deferred tax assets will not be realized. Tax rate changes are reflected in income during the period such changes areenacted. Changes in ownership may limit the amount of NOL carryforwards that can be utilized in the future to offset taxable income.Non-Cash Investing and Financing ActivitiesPurchases of property and equipment accrued in current liabilities amounted to $0.2 million, zero and $0.2 million for each of the years endedDecember 31, 2018, 2017 and 2016, respectively.Certain Risks and UncertaintiesThe Company’s products under development require approval from the FDA or other international regulatory agencies prior to commercial sales.There can be no assurance the products will receive the necessary clearance. If the Company is denied clearance or clearance is delayed, it may have amaterial adverse impact on the Company.The Company’s products are concentrated in rapidly-changing, highly-competitive markets, which are characterized by rapid technologicaladvances, changes in customer requirements and evolving regulatory requirements and industry standards. Any failure by the Company to anticipate or torespond adequately to technological developments in its industry, changes in customer requirements or changes in regulatory requirements or industrystandards or any significant delays in the development or introduction of products or services could have a material adverse effect on the Company’sbusiness, operating results and future cash flows.The Company depends on single source suppliers for critical raw materials for manufacturing, as well as other components required for theadministration of its products. The loss of these suppliers could delay the clinical trials or prevent or delay commercialization of the products.84Table of ContentsConcentrations of Credit RiskFinancial instruments, which potentially subject the Company to significant concentrations of credit risk, consist primarily of cash, cash equivalentsand marketable securities. The Company places its cash, cash equivalents and marketable securities with highly-rated financial institutions. At December 31,2018, the Company maintained all of its cash, cash equivalents and marketable securities in two financial institutions. Deposits held with these institutionsmay exceed the amount of insurance provided on such deposits. Generally, these deposits may be redeemed upon demand, and the Company believes there isminimal risk of losses on such balances.Segment and Geographic InformationThe Company operates in one reporting segment and, accordingly, no segment disclosures are presented herein. Foreign sales were not material foreach of the years ended December 31, 2018, 2017 and 2016.Recent Accounting PronouncementsIn August 2018, the U.S. Securities and Exchange Commission (SEC) adopted the final rule under SEC Release No. 33-10532, Disclosure Updateand Simplification. This final rule amends certain disclosure requirements that are redundant, duplicative, overlapping, outdated or superseded. In addition,the amendments expand the disclosure requirements on the analysis of stockholders' equity for interim financial statements. Under the amendments, ananalysis of changes in each caption of stockholders' equity presented in the balance sheet must be provided in a note or separate statement. The analysisshould present a reconciliation of the beginning balance to the ending balance of each period for which a statement of comprehensive income is required tobe filed. This final rule is effective for the Company for all filings made on or after November 5, 2018. The SEC staff clarified that the first presentation of thechanges in shareholders' equity may be included in the first Form 10-Q for the quarter that begins after the effective date of the amendments. The adoption ofthe final rule did not have a material impact on the Company’s consolidated financial statements. The Company will change its presentation of shareholder'sequity in the first quarter of 2019.In November 2016, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2016-18, Restricted Cash. Thenew standard requires that a statement of cash flows explain the change during the period in the total of cash, cash equivalents and amounts generallydescribed as restricted cash or restricted cash equivalents. Therefore, amounts generally described as restricted cash and restricted cash equivalents should beincluded with cash and cash equivalents when reconciling the beginning-of-period and end-of-period total amounts shown on the statement of cash flows.The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within annual periods beginning afterDecember 15, 2017. The Company adopted this new standard in the first quarter of 2018 and applied the provisions retrospectively. As a result of theadoption of the new guidance, the Company increased the beginning of year total amount shown on the consolidated statements of cash flows by $0.7million, $0.8 million, and $0.8 million for the years ended December 31, 2018, 2017 and 2016, equal to the balance of restricted cash included in theconsolidated balance sheets as of December 31, 2017, 2016 and 2015, respectively. Restricted cash relates primarily to amounts held as collateral for lettersof credit for leases for office space at the Company’s Washington, D.C. headquarters. As of December 31, 2018, restricted cash of $0.1 million and $0.6million is included in prepaid and other current assets and other non-current assets, respectively. As of December 31, 2017, restricted cash of $0.7 million isincluded in other non-current assets.In August 2016, the FASB issued ASU 2016-15, Statement of Cash Flows – Classification of Certain Cash Receipts and Cash Payments, to clarifyguidance on the classification of certain cash receipts and cash payments in the statement of cash flow. The standard is effective for annual reporting periodsbeginning after December 15, 2017, and interim periods within annual periods beginning after December 15, 2017. The Company’s adoption of this standardin the first quarter of 2018 had no impact to the Company’s consolidated financial statements.In June 2016, the FASB issued ASU 2016-13, Financial Instruments – Credit Losses, related to the measurement of credit losses on financialinstruments. The standard will require the use of an “expected loss” model for instruments measured at amortized cost. The standard is effective for yearsbeginning after December 15, 2019, and interim periods within annual periods beginning after December 15, 2019. The Company is evaluating this standardto determine if adoption will have a material impact on the Company’s consolidated financial statements.In February 2016, the FASB issued ASU 2016-2, Leases, which was further clarified by ASU 2018-10, Codification Improvements to Topic 842,Leases, and ASU 2018-11, Leases - Targeted Improvements, issued in July 2018. ASC 842 supersedes existing lease guidance, including ASC 840 - Leases.The new standard requires that lessees will need to recognize a right-of-use asset and a lease liability for virtually all of their leases (other than leases thatmeet the definition of a short-term85Table of Contentslease). The liability will be equal to the present value of lease payments. The asset will be based on the liability subject to certain adjustments. For incomestatement purposes, the FASB retained a dual model, requiring leases to be classified as either operating or finance. Operating leases will result in straight-line expense (similar to current operating leases) while finance leases will result in a front-loaded expense pattern (similar to current capital leases). TheCompany will adopt the new leasing standard in the first quarter of 2019 using the modified retrospective approach transition method through a cumulative-effect adjustment at the beginning of the period of adoption. Results for reporting periods beginning after January 1, 2019 will be presented under ASC 842,while prior period amounts are not adjusted and continue to be reported in accordance with historic accounting under ASC 840. The Company expects toelect the package of practical expedients permitted under the transition guidance within the standard, which eliminates the reassessment of past leases,classification and initial direct costs. The Company does not expect to elect the hindsight practical expedient. The Company expects that the adoption of thenew leasing standard will result in the recognition of material right-of-use asset and liabilities on the consolidated balance sheets for its operating leasecommitments with terms greater than twelve months.In May 2014, the FASB issued ASU 2014-9, Revenue from Contracts with Customers. This ASU supersedes the revenue recognition requirements inASC 605, Revenue Recognition, and creates ASC 606, Revenue from Contracts with Customers. ASC 606 requires companies to recognize revenue when ittransfers promised goods or services to customers in an amount that reflects the consideration to which a company expects to be entitled in exchange forthose goods or services. Under the new standard, revenue is recognized when a customer obtains control of a good or service. The standard allows for twotransition methods—entities can either apply the new standard (i) retrospectively to each prior reporting period presented (full retrospective), or(ii) retrospectively with the cumulative effect of initially applying the standard recognized at the date of initial adoption (modified retrospective). In July2015, the FASB issued ASU 2015-14, Revenue from Contracts with Customers, which defers the effective date by one year to December 15, 2017 for fiscalyears, and interim periods within those fiscal years, beginning after that date. Early adoption of the standard is permitted, but not before the original effectivedate of December 15, 2016. In March 2016, the FASB issued ASU 2016-8 Revenue from Contracts with Customers, Principal versus Agent Considerations(Reporting Revenue versus Net), in April 2016, the FASB issued ASU 2016-10, Revenue from Contracts with Customers, identifying PerformanceObligations and Licensing, and in May 2016, the FASB issued ASU 2016-12, Revenue from Contracts with Customers, Narrow-Scope Improvements andPractical Expedients, which provide additional clarification on certain topics addressed in ASU 2014-9. ASU 2016-8, ASU 2016-10, and ASU 2016-12 followthe same implementation guidelines as ASU 2014-9 and ASU 2015-14. The Company adopted this new standard in the first quarter of 2018 using themodified retrospective method to those contracts which were not completed as of January 1, 2018. Results for reporting periods beginning after January 1,2018 are presented under ASC 606, while prior period amounts are not adjusted and continue to be reported in accordance with historic accounting underASC 605. There was no impact to opening retained earnings as of January 1, 2018 as a result of adoption of the new standard. The impact to the consolidatedstatements of operations if the Company had applied ASC 605 for the years ended December 31, 2017 and 2016 is not material. As a result of adoption, theCompany reclassified the provision for product revenue returns of $5.2 million from accounts receivable, net to product revenue allowances and other non-current liabilities in the consolidated balance sheets as of December 31, 2018. The provision for product returns as of December 31, 2017 of $4.1 million isincluded in accounts receivable in the consolidated balance sheet.3. Marketable SecuritiesThe following is a summary of the Company’s available-for-sale marketable securities as of December 31, 2018, all of which have contract maturitiesof less than one year:December 31, 2018(in thousands)AmortizedCost GrossUnrealizedGains GrossUnrealizedLosses FairMarketValueU.S. Treasury and government agencies$69,275 $12 $(17) $69,270Corporate debt105,897 38 (25) 105,910Asset-backed securities21,189 — (14) 21,175 $196,361$50$(56)$196,35586Table of ContentsThe following is a summary of the Company’s available-for-sale marketable securities as of December 31, 2017:December 31, 2017(in thousands)Amortized Cost GrossUnrealizedGains GrossUnrealizedLosses FairMarketValueU.S. Treasury and government agencies$60,681 $— $(63) $60,618Corporate debt49,168 12 (12) 49,168 $109,849$12$(75)$109,786 4. Fair Value MeasurementsAuthoritative guidance establishes a three-tier fair value hierarchy, which prioritizes the inputs used in measuring fair value. These tiers include: •Level 1 — defined as observable inputs such as quoted prices in active markets •Level 2 — defined as inputs other than quoted prices in active markets that are either directly or indirectly observable •Level 3 — defined as unobservable inputs in which little or no market data exists, therefore requiring an entity to develop its own assumptions Marketable securities classified in Level 1 and Level 2 as of December 31, 2018 and 2017 consist of cash equivalents and available-for-salemarketable securities. The valuation of Level 1 instruments is determined using a market approach, and is based upon unadjusted quoted prices for identicalassets in active markets. The valuation of investments classified in Level 2 also is determined using a market approach based upon quoted prices for similarassets in active markets, or other inputs that are observable for substantially the full term of the financial instrument. Level 2 securities include certificates ofdeposit, commercial paper and corporate notes that use as their basis readily observable market parameters. The Company did not transfer any assets betweenLevel 2 and Level 1 during the years ended December 31, 2018 and 2017. The Company held certain assets that are required to be measured at fair value on a recurring basis as of December 31, 2018, as follows: Fair Value Measurement as of December 31, 2018 Using(in thousands)December 31, 2018 Quoted Prices inActive Markets forIdentical Assets(Level 1) Significant OtherObservable Inputs(Level 2) SignificantUnobservableInputs(Level 3)U.S. Treasury and government agencies69,270 69,270 — —Corporate debt105,910 — 105,910 —Asset-backed securities21,175 — 21,175 — $196,355$69,270$127,085$—The Company held certain assets that are required to be measured at fair value on a recurring basis as of December 31, 2017, as follows: Fair Value Measurement as of December 31, 2017 Using(in thousands)December 31, 2017 Quoted Prices inActive Markets forIdentical Assets(Level 1) Significant OtherObservable Inputs(Level 2) SignificantUnobservableInputs(Level 3)U.S. Treasury and government agencies$60,618 $60,618 $— $—Corporate debt53,164 — 53,164 — $113,782$60,618$53,164$—Total assets measured at fair value as of December 31, 2017 include $4.0 million of cash equivalents.The Company also has financial assets and liabilities, not required to be measured at fair value on a recurring basis, which primarily consist of cashand cash equivalents, accounts receivable, restricted cash, accounts payable and accrued87Table of Contentsliabilities, and milestone obligations under license agreements, the carrying values of which materially approximate their fair values.5. InventoryThe Company evaluates expiry risk by evaluating current and future product demand relative to product shelf life. The Company builds demandforecasts by considering factors such as, but not limited to, overall market potential, market share, market acceptance and patient usage. Inventory levels areevaluated for the amount of inventory that would be sold within one year. At certain times, the level of inventory can exceed the forecasted level of cost ofgoods sold for the next twelve months. The Company classifies the estimate of such inventory as non-current. Inventory consisted of the following as ofDecember 31, 2018 and 2017:(in thousands)December 31, 2018 December 31, 2017Current assets Work-in-process$48 $80Finished goods946 760 $994 $840Non-Current assets Raw materials$86 $87Work-in-process2,290 2,821Finished goods516 408 $2,892 $3,316 6. Property and EquipmentThe following is a summary of the Company’s property and equipment, at cost, as of December 31, 2018 and 2017:(in thousands)EstimatedUseful Life(Years) December 31, 2018 December 31, 2017Computer and other equipment3 $3,642 $3,342Furniture and fixtures5 - 7 1,488 1,929Leasehold improvements5 - 11 4,506 4,515 9,636 9,786Accumulated depreciation and amortization (5,219) (4,480) $4,417 $5,306 Depreciation expense was $1.4 million, $1.2 million and $0.9 million for the years ended December 31, 2018, 2017 and 2016, respectively. 7. Intangible AssetsHETLIOZ®. In January 2014, the Company announced that the FDA had approved the New Drug Application (NDA) for HETLIOZ®. As a result ofthis approval, the Company met a milestone under its license agreement with Bristol-Myers Squibb (BMS) that required the Company to make a licensepayment of $8.0 million to BMS. The $8.0 million is being amortized on a straight-line basis over the estimated economic useful life of the related productpatents, the latest of which expires in February 2035. The estimated economic useful life of the intangible asset was changed from May 2034 to February2035 based on the February 2035 expiration date of U.S. patent number 10,071,977 ('977 patent) issued by the U.S. Patent and Trademark Office inSeptember 2018.In April 2018, the Company met its final milestone under its license agreement when cumulative worldwide sales of HETLIOZ® reached $250.0million. As a result of the achievement of this milestone, the Company made a payment to BMS of $25.0 million in 2018. The $25.0 million obligation wasrecorded as a current liability as of December 31, 2017. The $25.0 million was determined to be additional consideration for the acquisition of theHETLIOZ® intangible asset and is being amortized on a straight-line basis over the estimated economic useful life of the related product patents, the latest ofwhich expires in February 2035. The estimated economic useful life of the intangible asset was changed from May 2034 to February88Table of Contents2035 based on the February 2035 expiration date of the '977 patent issued by the U.S. Patent and Trademark Office in September 2018.Fanapt®. In 2009, the Company announced that the FDA had approved the NDA for Fanapt®. As a result of this approval, the Company met amilestone under its original sublicense agreement with Novartis that required the Company to make a license payment of $12.0 million to Novartis. The$12.0 million was amortized on a straight-line basis over the remaining life of the U.S. composition of matter patent for Fanapt® to November 2016.Pursuant to a settlement agreement entered into in December 2014, Novartis transferred all U.S. and Canadian rights in the Fanapt® franchise to theCompany. As a result, the Company recognized an intangible asset of $15.9 million on December 31, 2014 related to the reacquired rights to Fanapt®, whichwas fully amortized on a straight-line basis as of November 2016. The useful life estimation for the Fanapt® intangible asset was based on the marketparticipant methodology prescribed by ASC 805, and therefore does not reflect the impact of additional Fanapt® patents solely owned by the Company withvarying expiration dates, the latest of which is December 2031.The following is a summary of the Company’s intangible assets as of December 31, 2018: December 31, 2018(in thousands)EstimatedUseful Life(Years) GrossCarryingAmount AccumulatedAmortization NetCarryingAmountHETLIOZ®February 2035 $33,000 $8,458 $24,542Fanapt®November 2016 27,941 27,941 — $60,941 $36,399 $24,542The following is a summary of the Company’s intangible assets as of December 31, 2017: December 31, 2017(in thousands)EstimatedUseful Life(Years) GrossCarryingAmount AccumulatedAmortization NetCarryingAmountHETLIOZ®May 2034 $33,000 $6,931 $26,069Fanapt®November 2016 27,941 27,941 — $60,941 $34,872 $26,069Intangible assets are amortized over their estimated useful economic life using the straight-line method. Amortization expense for the years endedDecember 31, 2018, 2017 and 2016 was as follows: Year Ended December 31,(in thousands)2018 2017 2016HETLIOZ®$1,527 $1,750 $1,721Fanapt®— — 9,212 $1,527 $1,750 $10,933The following is a summary of the future intangible asset amortization schedule as of December 31, 2018:(in thousands)Total 2019 2020 2021 2022 2023 ThereafterHETLIOZ®$24,542 $1,518 $1,518 $1,518 $1,518 $1,518 $16,95289Table of Contents8. Accounts Payable and Accrued LiabilitiesThe following is a summary of the Company’s accounts payable and accrued liabilities as of December 31, 2018 and 2017:(in thousands)December 31, 2018 December 31, 2017Compensation and employee benefits$6,363 $5,323Research and development expenses5,593 4,663Royalties payable5,172 4,394Consulting and other professional fees2,924 3,961Other1,532 1,994 $21,584 $20,3359. Commitments and ContingenciesThe following is a summary of the Company's noncancellable long-term contractual cash obligations as of December 31, 2018: Cash Payments Due by Year(in thousands)Total 2019 2020 2021 2022 2023 ThereafterOperating leases$22,757 $2,483 $2,495 $2,335 $2,355 $2,420 $10,669Milestone obligations200 200 — — — — —Purchase commitments7,315 5,122 847 890 456 — — $30,272 $7,805 $3,342 $3,225 $2,811 $2,420 $10,669Operating LeasesCommitments relating to operating leases represent the minimum annual future payments under operating leases and subleases for its Company'sheadquarters at 2200 Pennsylvania Avenue, N.W. in Washington, D.C., and operating leases for office space in London and Berlin.In June 2011, the Company entered into an operating lease for its headquarters at 2200 Pennsylvania Avenue, N.W. in Washington, D.C. for 21,400square feet of office space. The Company subsequently amended the lease in March 2014 and March 2018 to increase the office space under lease to 33,534square feet and, in March 2018, extended the lease term to July 2028. Subject to the prior rights of other tenants, the Company has the right to renew the leasefor five years following its expiration. The Company has the right to sublease or assign all or a portion of the premises, subject to standard conditions. Thelease may be terminated early by the Company or the landlord under certain circumstances.In June 2016, the Company entered into a sublease under which the Company leases 9,928 square feet of office space for its headquarters at 2200Pennsylvania Avenue, N.W. in Washington, D.C. The sublease term began in January 2017 and ends in July 2026, but may be terminated earlier by eitherparty under certain circumstances. The Company has the right to sublease or assign all or a portion of the premises, subject to standard conditions.The Company has an operating lease for 2,880 square feet of office space for the Company’s European headquarters in London that has anoncancellable lease term ending in 2021, and 1,249 square feet of office space in Berlin under a short-term operating lease.Rent expense under operating leases and subleases was $3.6 million, $3.2 million and $2.5 million for the years ended December 31, 2018, 2017and 2016, respectively.Guarantees and IndemnificationsThe Company has entered into a number of standard intellectual property indemnification agreements in the ordinary course of its business.Pursuant to these agreements, the Company indemnifies, holds harmless, and agrees to reimburse the indemnified party for losses suffered or incurred by theindemnified party, generally the Company’s business partners or customers, in connection with any U.S. patent or any copyright or other intellectual propertyinfringement claim by any third90Table of Contentsparty with respect to the Company’s products. The term of these indemnification agreements is generally perpetual from the date of execution of theagreement. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is unlimited.Since inception, the Company has not incurred costs to defend lawsuits or settle claims related to these indemnification agreements. The Company alsoindemnifies its officers and directors for certain events or occurrences, subject to certain conditions.License AgreementsThe Company’s rights to develop and commercialize its products are subject to the terms and conditions of licenses granted to the Company byother pharmaceutical companies.HETLIOZ®. In February 2004, the Company entered into a license agreement with BMS under which it received an exclusive worldwide licenseunder certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize HETLIOZ®. As a result of the FDA’sapproval of the HETLIOZ® NDA in January 2014, the Company made an $8.0 million milestone payment to BMS in the first quarter of 2014 under thelicense agreement that was capitalized as an intangible asset and is being amortized over the estimated economic useful life of the related product patents forHETLIOZ® in the U.S. In April 2018, the Company met another milestone under its license agreement when cumulative worldwide sales ofHETLIOZ® reached $250.0 million. As a result of the achievement of this milestone, the Company made a payment to BMS of $25.0 million in the secondquarter of 2018. The $25.0 million milestone obligation was capitalized as an intangible asset in the first quarter of 2015 and is being amortized over theestimated economic useful life of the related product patents for HETLIOZ® in the U.S. The Company has no remaining milestone obligations to BMS.Additionally, the Company is obligated to make royalty payments on HETLIOZ® net sales to BMS in any territory where the Company commercializesHETLIOZ® for a period equal to the greater of 10 years following the first commercial sale in the territory or the expiry of the new chemical entity (NCE)patent in that territory. During the period prior to the expiry of the NCE patent in a territory, the Company is obligated to pay a 10% royalty on net sales inthat territory. The royalty rate is decreased by half for countries in which no NCE patent existed or for the remainder of the 10 years after the expiry of theNCE patent. The Company is also obligated under the license agreement to pay BMS a percentage of any sublicense fees, upfront payments and milestoneand other payments (excluding royalties) that it receives from a third party in connection with any sublicensing arrangement, at a rate which is in the mid-twenties. The Company has agreed with BMS in the license agreement for HETLIOZ® to use its commercially reasonable efforts to develop andcommercialize HETLIOZ®.Fanapt®. Pursuant to the terms of a settlement agreement with Novartis, Novartis transferred all U.S. and Canadian rights in the Fanapt® franchise tothe Company on December 31, 2014. The Company was obligated to make royalty payments to Sanofi S.A. (Sanofi) and Titan Pharmaceuticals Inc. (Titan) ata percentage rate equal to 23% on annual U.S. net sales of Fanapt® up to $200.0 million, and at a percentage rate in the mid-twenties on sales over $200.0million through November 2016. In February 2016, the Company amended the agreement with Sanofi and Titan to remove Titan as the entity through whichroyalty payments from the Company are directed to Sanofi following the expiration of the new chemical entity patent for Fanapt® in the U.S. onNovember 15, 2016. Under the amended agreement, the Company pays directly to Sanofi a fixed royalty of 3% of net sales from November 16, 2016 throughDecember 31, 2019 related to manufacturing know-how. The Company made a $2.0 million payment during the year ended December 31, 2016 that appliedto this 3% manufacturing know-how royalty. No further royalties on manufacturing know-how are payable by the Company after December 31, 2019. Thisamended agreement did not alter Titan’s obligation under the license agreement to make royalty payments to Sanofi prior to November 16, 2016 or theCompany’s obligations to pay Sanofi a fixed royalty on Fanapt® net sales equal up to 6% on Sanofi know-how not related to manufacturing under certainconditions for a period of up to 10 years in markets where the new chemical entity patent has expired or was not issued.Tradipitant. In April 2012, the Company entered into a license agreement with Eli Lilly and Company (Lilly) pursuant to which the Companyacquired an exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop andcommercialize an NK-1R antagonist, tradipitant, for all human indications. The patent describing tradipitant as a NCE expires in April 2023, except in theU.S., where it expires in June 2024 absent any applicable patent term adjustments. Lilly is eligible to receive future payments based upon achievement ofspecified development and commercialization milestones as well as tiered-royalties on net sales at percentage rates up to the low double digits. Thesemilestones include $4.0 million for pre-NDA approval milestones, $10.0 million and $5.0 million for the first approval of a marketing authorization fortradipitant in the U.S. and European Union (E.U.), respectively, and up to $80 million for sales milestones. The $4.0 million of pre-NDA approval milestonesincludes $2.0 million due upon enrollment of the first subject into a Phase III study for tradipitant and $2.0 million due upon the filing of the first marketingauthorization for tradipitant in either the U.S. or the E.U. As a result of enrolling the first subject into a Phase III study for tradipitant in July 2018, theCompany made a $2.0 million milestone payment to Lilly in the third quarter of 2018. The likelihood of achieving this milestone was determined to beprobable during 2017 and the obligation of $2.0 million tied to such milestone was91Table of Contentsrecorded as research and development expense in the consolidated statement of operations during the year ended December 31, 2017 and a current liabilityin the consolidated balance sheet as of December 31, 2017. The Company is obligated to use its commercially reasonable efforts to develop andcommercialize tradipitant.VQW-765. In connection with a settlement agreement with Novartis relating to Fanapt®, the Company received an exclusive worldwide licenseunder certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7nicotinic acetylcholine receptor partial agonist. Pursuant to the license agreement, the Company is obligated to use its commercially reasonable efforts todevelop and commercialize VQW-765 and is responsible for all development costs. The Company has no milestone obligations; however, Novartis is eligibleto receive tiered-royalties on net sales at percentage rates up to the mid-teens.Portfolio of CFTR activators and inhibitors. In March 2017, the Company entered into a license agreement with the University of California SanFrancisco (UCSF), under which Vanda acquired an exclusive worldwide license to develop and commercialize a portfolio of CFTR activators and inhibitors.Pursuant to the license agreement, the Company will develop and commercialize the CFTR activators and inhibitors and is responsible for all developmentcosts under the license agreement, including current pre-investigational new drug development work. UCSF is eligible to receive future payments based uponachievement of specified development and commercialization milestones as well as single-digit royalties on net sales. These milestones include an initiallicense fee of $1.0 million that was paid by the Company in 2017, annual maintenance fees, $12.4 million for pre-NDA approval milestones and $33.0million for future regulatory approval and sales milestones. Included in the $12.4 million in pre-NDA approval milestones is a $350,000 milestone due uponthe conclusion of a Phase I study for each licensed product but not to exceed $1.1 million in total for the CFTR portfolio. In the fourth quarter of 2018, theCompany determined the first pre-NDA approval milestone to be probable and accrued a current liability of $0.2 million as of December 31, 2018.Purchase CommitmentsIn the course of its business, the Company regularly enters into agreements with clinical organizations to provide services relating to clinicaldevelopment and clinical manufacturing activities under fee service arrangements. The Company’s current agreements for clinical and marketing servicesmay be terminated on generally 90 days’ notice without incurring additional charges, other than charges for work completed but not paid for through theeffective date of termination and other costs incurred by the Company’s contractors in closing out work in progress as of the effective date of termination.Purchase commitments included in the noncancellable long-term contractual cash obligations table above include noncancellable purchase commitmentslonger than one year and primarily relate to commitments for advertising and data services.10. Public Offering of Common StockIn March 2018, the Company completed a public offering of 6,325,000 shares of its common stock, including the exercise of the underwriters’option to purchase an additional 825,000 shares of common stock, at a price to the public of $17.00 per share. Net cash proceeds from the public offeringwere $100.9 million, after deducting the underwriting discounts and commissions and offering expenses.11. Accumulated Other Comprehensive Income (Loss)The accumulated balances related to each component of other comprehensive income (loss) were as follows for the years ended December 31, 2018and 2017:(in thousands)December 31, 2018 December 31, 2017Foreign currency translation$7 $29Available-for-sale securities(6) (63) $1 $(34)There were no reclassifications out of accumulated other comprehensive income (loss) for the years ended December 31, 2018, 2017 and 2016.12. Stock-Based CompensationAs of December 31, 2018, there were 5,682,618 shares that were subject to outstanding options and restricted stock units (RSUs) under the 2006Equity Incentive Plan (2006 Plan) and the Amended and Restated 2016 Equity Incentive Plan92Table of Contents(2016 Plan, and together with the 2006 Plan, Plans). The 2006 Plan expired by its terms on April 12, 2016, and the Company adopted the 2016 Plan.Outstanding options and RSUs under the 2006 Plan remain in effect and the terms of the 2006 Plan continue to apply, but no additional awards can begranted under the 2006 Plan. In June 2016, the Company’s stockholders approved the 2016 Plan. The 2016 Plan has been amended and restated twice toincrease the number of shares reserved for issuance, among other administrative changes. Both amendments and restatements of the 2016 Plan were approvedby the Company's stockholders. There are a total of 7,100,000 shares of common stock reserved for issuance under the 2016 Plan, 4,576,126 shares of whichremained available for future grant as of December 31, 2018.Stock OptionsThe Company has granted option awards under the Plans with service conditions (service option awards) that are subject to terms and conditionsestablished by the compensation committee of the board of directors. Service option awards have 10-year contractual terms and all service option awardsgranted prior to December 31, 2006, service option awards granted to new employees, and certain service option awards granted to existing employees vestand become exercisable on the first anniversary of the grant date with respect to the 25% of the shares subject to service option awards. The remaining 75% ofthe shares subject to the service option awards vest and become exercisable monthly in equal installments thereafter over three years. Certain service optionawards granted to existing employees after December 31, 2006 vest and become exercisable monthly in equal installments over four years. The initial serviceoption awards granted to directors upon their election vest and become exercisable in equal monthly installments over a period of four years, while thesubsequent annual service option awards granted to directors vest and become exercisable in equal monthly installments over a period of one year. Certainservice option awards to executives and directors provide for accelerated vesting if there is a change in control of the Company. Certain service optionawards to employees and executives provide for accelerated vesting if the respective employee’s or executive’s service is terminated by the Company for anyreason other than cause or permanent disability.As of December 31, 2018, $7.2 million of unrecognized compensation costs related to unvested service option awards are expected to be recognizedover a weighted average period of 1.4 years. No option awards are classified as a liability as of December 31, 2018.The following is a summary of option activity for the 2006 Plan and the 2016 Plan for the years ended December 31, 2018, 2017, and 2016:2006 and 2016 Plans(in thousands, except for share and per share amounts)Number ofShares Weighted AverageExercise Price at GrantDate Weighted AverageRemaining Term(Years) AggregateIntrinsicValueOutstanding at December 31, 20156,252,448 $11.87 6.16 $7,498Granted866,011 8.43 Forfeited(392,700) 11.23 Expired(279,766) 17.38 Exercised(897,657) 8.63 4,264Outstanding at December 31, 20165,548,336 11.62 5.58 32,453Granted643,000 14.44 Forfeited(290,729) 10.73 Expired(605,617) 29.87 Exercised(575,206) 9.13 3,140Outstanding at December 31, 20174,719,784 10.03 5.63 24,421Granted567,500 19.22 Forfeited(232,527) 13.99 Exercised(685,715) 9.12 5,945Outstanding at December 31, 20184,369,042 11.15 5.28 65,438Exercisable at December 31, 20183,487,495 10.01 4.48 56,222Vested and expected to vest at December 31, 20184,248,680 10.96 5.18 64,466The weighted average grant-date fair value of options granted was $10.66, $7.81 and $4.53 per share for the years ended December 31, 2018, 2017and 2016, respectively. Proceeds from the exercise of stock options amounted to $6.3 million, $5.3 million and $7.8 million for the years endedDecember 31, 2018, 2017 and 2016, respectively.93Table of ContentsRestricted Stock UnitsAn RSU is a stock award that entitles the holder to receive shares of the Company’s common stock as the award vests. The fair value of each RSU isbased on the closing price of the Company’s stock on the date of grant. The Company has granted RSUs under the Plans with service conditions (serviceRSUs) that vest in four equal annual installments provided that the employee remains employed with the Company. Annual service RSUs granted to directorsvest on the first anniversary of the grant date.As of December 31, 2018, $14.9 million of unrecognized compensation costs related to unvested service RSUs are expected to be recognized over aweighted average period of 1.8 years. No RSUs are classified as a liability as of December 31, 2018.The following is a summary of RSU activity for the 2006 Plan and the 2016 Plan for the years ended December 31, 2018, 2017, and 2016:RSUsNumber ofShares WeightedAverageGrant DateFair ValueUnvested at December 31, 20151,022,681 $10.90Granted657,742 8.71Forfeited(254,329) 10.38Vested(287,666) 9.65Unvested at December 31, 20161,138,428 10.07Granted857,336 14.57Forfeited(275,613) 11.41Vested(362,313) 9.78Unvested at December 31, 20171,357,838 12.72Granted714,086 18.93Forfeited(229,603) 15.19Vested(528,745) 12.69Unvested at December 31, 20181,313,576 15.68The grant date fair value for the 528,745 shares underlying RSUs that vested during the year ended December 31, 2018 was $6.7 million.Stock-Based Compensation ExpenseStock-based compensation expense recognized for the years ended December 31, 2018, 2017 and 2016 was allocated as follows: Year Ended December 31,(in thousands)2018 2017 2016Research and development$1,290 $1,152 $2,087Selling, general and administrative10,376 9,313 6,456 $11,666 $10,465 $8,543The fair value of each option award is estimated on the date of grant using the Black-Scholes-Merton option pricing model that uses the assumptionsnoted in the following table. Expected volatility rates are based on the historical volatility of the Company’s publicly traded common stock and otherfactors. The risk-free interest rates are based on the U.S. Treasury yield for a period consistent with the expected term of the option in effect at the time of thegrant. The Company has not paid dividends to its stockholders since its inception (other than a dividend of preferred share purchase rights, which wasdeclared in September 2008) and does not plan to pay dividends in the foreseeable future. Assumptions used in the Black-Scholes-Merton option pricingmodel for employee and director stock options granted during the years ended December 31, 2018, 2017 and 2016 were as follows:94Table of Contents Year Ended December 31, 2018 2017 2016Expected dividend yield—% —% —%Weighted average expected volatility58% 57% 57%Weighted average expected term (years)5.90 5.89 6.08Weighted average risk-free rate2.68% 1.97% 1.37%13. Employee Benefit PlanThe Company has a defined contribution plan under IRC Section 401(k). This plan covers substantially all employees who meet minimum age andservice requirements and allows participants to defer a portion of their annual compensation on a pre-tax basis. Currently, the Company matches fifty percentup to the first six percent of employee contributions. All matching contributions have been paid by the Company. The Company match vests over a 4-yearperiod and amounted to $0.9 million, $0.8 million and $0.4 million for the years ended December 31, 2018, 2017 and 2016, respectively.14. Income TaxesThe Company recorded total tax expense of $0.1 million on consolidated pretax income of $25.3 million, consisting of $25.1 million and $0.2million of pretax income in the U.S. and foreign subsidiaries, respectively, for the year ended December 31, 2018. The Company recorded total tax expense of$0.1 million on consolidated pretax loss of $15.4 million, consisting of $15.7 million of pretax loss in the U.S. and $0.3 million of pretax income fromforeign subsidiaries for the year ended December 31, 2017. The Company recorded total tax expense of $0.1 million on consolidated pretax loss of $17.9million, consisting of $18.1 million of pretax loss in the U.S. and $0.2 million of pretax income from foreign subsidiaries for the year ended December 31,2016.The following is a summary of the provision (benefit) for income taxes for the years ended December 31, 2018, 2017 and 2016: Year Ended December 31,(in thousands)2018 2017 2016Current: Federal$— $— $—State53 65 66Foreign99 (66) 142Deferred: Federal— — —State— — —Foreign(14) 137 (104)Provision for income taxes$138 $136 $104The Company assesses the need for a valuation allowance against its deferred tax asset each quarter through the review of all available positive andnegative evidence. Deferred tax assets are reduced by a tax valuation allowance when, in the opinion of management, it is more likely than not that someportion or all of the deferred tax assets will not be realized. The fact that the Company has historically generated pretax losses in the U.S. serves as strongevidence that it is more likely than not that deferred tax assets in the U.S. will not be realized in the future. Therefore, the Company had a full tax valuationallowance against all net deferred tax assets in the U.S. as of December 31, 2018 and 2017. A reduction of the valuation allowance, in whole or in part, wouldresult in a non-cash income tax benefit during the period of reduction. The potential timing and amount of any future valuation allowance release has yet tobe determined and requires an analysis that is highly dependent upon historical and future projected earnings, among other factors. Any such adjustmentcould have a material impact on the Company’s finance position and results of operations.95Table of ContentsAs a result of the tax valuation allowance against deferred tax assets in the U.S., there was no expense (benefit) for income taxes associated with theU.S. income (loss) before income taxes for each of the years ended December 31, 2018, 2017 and 2016. The following is reconciliation between the federalstatutory tax rate and the Company’s effective tax rate for the years ended December 31, 2018, 2017 and 2016: Year Ended December 31, 2018 2017 2016Federal tax at statutory rate21.0 % 35.0 % 35.0 %State taxes1.7 % 1.7 % 0.8 %U.S. Tax Cuts and Job Act (1)0.0 % -262.6 % 0.0 %Change in valuation allowance - U.S. Tax Cuts and Jobs Act0.0 % 262.6 % 0.0 %Other change in valuation allowance (2)-16.4 % -47.8 % -38.4 %Research and development credit-9.1 % 9.0 % 3.8 %Orphan drug credit-2.7 % 6.3 % 7.6 %Section 162(m) limitation3.1 % 8.1 % 0.0 %Other tax rate changes-0.7 % -2.6 % 3.9 %Other changes in state deferred taxes (3)5.9 % 5.1 % 0.0 %Stock-based compensation-3.9 % -13.0 % -12.5 %Other items1.6 % -2.7 % -0.8 %Effective tax rate0.5 %-0.9 %-0.6 % (1)Includes the effect of the Tax Cuts and Jobs Act, which primarily relates to the remeasurement of existing deferred taxes as a result of the change tothe U.S. federal tax rate.(2)Reductions in 2018 valuation allowances are attributable to profitable 2018 U.S. results.(3)Includes adjustments to state deferred taxes based on changes to filing jurisdictions.The following is a summary of the components of the Company’s deferred tax liabilities, net, and the related tax valuation allowance as ofDecember 31, 2018 and 2017:(in thousands)December 31, 2018 December 31, 2017Deferred tax assets: Net operating loss carryforwards$55,742 $59,222Stock-based compensation5,202 5,383Accrued and deferred expenses2,096 1,967Allowance for returns and uncollectable receivables1,247 1,051Research and development and orphan drug credit carryforwards48,066 43,976Intangible assets— 3,745Other1,405 1,123Total deferred tax assets113,758 116,467Deferred tax liabilities: Intangible assets(1,247) —Other(576) (386)Total deferred tax liabilities(1,823) (386)Deferred tax assets, net111,935 116,081Valuation allowance111,950 116,110Net deferred tax assets (liabilities)$(15) $(29)The Company’s net deferred tax liability of less than $0.1 million as of December 31, 2018 and 2017 is included as a component of other non-current liabilities.96Table of ContentsThe following is a summary of changes in the Company’s tax valuation allowance for the years ended December 31, 2018, 2017 and 2016:(in thousands)Balance atBeginningof Year Additions Reductions Balance atEnd ofYearYear Ended: December 31, 2018$116,110 $4,036 $(8,196) $111,950December 31, 2017146,012 12,403 (42,305) 116,110December 31, 2016139,037 11,031 (4,056) 146,012The Company has net operating loss (NOL) and other tax credit carryforwards in several jurisdictions. As of December 31, 2018, the Company has$46.7 million of deferred tax assets relating to U.S. federal NOL carryforwards, along with deferred tax assets of $12.1 million and $36.0 million related toU.S. federal research and development credits and orphan drug credits, respectively. These tax attributes will begin to expire in 2029, 2024 and 2030,respectively. In addition, the Company has $9.0 million of deferred tax assets relating to U.S. state NOL carryforwards, which primarily relate to the District ofColumbia. State NOLs for the District of Columbia will begin to expire in 2031 and other state NOLs will begin to expire in 2019. A valuation allowance isrecorded against these U.S. federal and U.S. state deferred tax assets.Because the Company has generated or utilized NOLs from inception through December 31, 2018, all income tax returns filed by the Company areopen to examination by tax jurisdictions. As of December 31, 2018, the Company’s income tax returns had not been under examination by any federal orstate tax jurisdictions. As of December 31, 2018 and 2017, the Company had no uncertain tax positions.Certain tax attributes of the Company, including NOLs and credits, would be subject to a limitation should an ownership change as defined underthe Internal Revenue Code of 1986, as amended (IRC), Section 382, occur. The limitations resulting from a change in ownership could affect the Company’sability to utilize its NOLs and credit carryforward (tax attributes). Ownership changes occurred in the years ending December 31, 2014 and December 31,2008. The Company believes that the ownership changes in 2014 and 2008 will not impact its ability to utilize NOL and credit carryforwards; however,future ownership changes may cause the Company’s existing tax attributes to have additional limitations. Because the Company maintains a valuationallowance on its U.S. tax attributes, any limitation as a result of application of IRC Section 382 limitation would not have a material impact on theCompany’s provision for income taxes for the year ended December 31, 2018.The Tax Cuts and Jobs Act (TCJA) was enacted in December 2017. The TCJA reduces the U.S. federal corporate tax rate from 35% to 21%, requirescompanies to pay a one-time transition tax on earnings of certain foreign subsidiaries that were previously deferred and creates new taxes on certain foreignsourced earnings. During the fourth quarter of 2018, the Company completed its accounting for the tax effects of the TCJA. No material measurement periodadjustments were recorded in 2018 to adjust estimated effects of the Act that were recorded in 2017. Immaterial measurement period adjustments that wererecorded resulted in no tax expense as they were fully offset by a change in the Company's valuation allowance.15. Earnings per ShareBasic earnings per share (EPS) is calculated by dividing the net loss by the weighted average number of shares of common stock outstanding.Diluted EPS is computed by dividing the net loss by the weighted average number of shares of common stock outstanding, plus potential outstandingcommon stock for the period. Potential outstanding common stock includes stock options and shares underlying RSUs, but only to the extent that theirinclusion is dilutive. 97Table of ContentsThe following table presents the calculation of basic and diluted net income (loss) per share of common stock for the years ended December 31,2018, 2017 and 2016: Year Ended December 31,(in thousands, except for share and per share amounts)2018 2017 2016Numerator: Net income (loss)$25,208 $(15,567) $(18,010)Denominator: Weighted average shares outstanding, basic50,859,947 44,735,146 43,449,441Effect of dilutive securities2,185,310 — —Weighted average shares outstanding, diluted53,045,257 44,735,146 43,449,441Net income (loss) per share, basic and diluted: Basic$0.50 $(0.35) $(0.41)Diluted$0.48 $(0.35) $(0.41)Antidilutive securities excluded from calculations of diluted net income (loss) per share903,265 3,136,515 4,943,797The Company incurred a net loss for each of the years ended December 31, 2017 and 2016 causing inclusion of any potentially dilutive securities tohave an anti-dilutive effect, resulting in dilutive loss per share and basic loss per share attributable to common stockholders being equivalent.16. Legal MattersFanapt®. In June 2014, the Company filed suit against Roxane Laboratories, Inc. (Roxane) in the U.S. District Court for the District of Delaware(Delaware District Court). The suit sought an adjudication that Roxane has infringed one or more claims of the Company's U.S. Patent No. 8,586,610 (‘610Patent) by submitting to the U.S. Food and Drug Administration (FDA) an Abbreviated New Drug Application (ANDA) for a generic version of Fanapt® priorto the expiration of the ‘610 Patent in November 2027. In addition, pursuant to a settlement agreement with Novartis Pharma AG (Novartis), the Companyassumed Novartis’ patent infringement action against Roxane in the Delaware District Court. That suit alleges that Roxane has infringed one or more claimsof U.S. Patent RE39198 (‘198 Patent), which is licensed exclusively to the Company, by filing an ANDA for a generic version of Fanapt® prior to theexpiration of the ‘198 Patent in November 2016. These two cases against Roxane were consolidated by agreement of the parties and were tried together ina five-day bench trial that concluded in March 2016. In August 2016, the Delaware District Court ruled that the Company is entitled to a permanentinjunction against Roxane enjoining Roxane from infringing the ‘610 Patent, including the manufacture, use, sale, offer to sell, sale, distribution orimportation of any generic iloperidone product described in the ‘610 Patent ANDA until the expiration of the ‘610 Patent in November 2027. If the Companyobtains pediatric exclusivity, the injunction against Roxane would be extended until May 2028 under the Delaware District Court’s order. In September2016, Roxane filed a notice of appeal with the Federal Circuit Court of Appeals (Federal Circuit). In July 2017, Roxane, now a subsidiary of HikmaPharmaceuticals PLC (Hikma), petitioned the Federal Circuit to substitute Roxane with new defendants West-Ward Pharmaceuticals International Limitedand West-Ward Pharmaceuticals Corp. (each of which is a subsidiary of Hikma and both of which are referred to collectively herein as West-Ward). In April2018, the Federal Circuit affirmed the Delaware District Court’s decision that West-Ward infringed the ‘610 Patent. In June 2018, West-Ward filed with theFederal Circuit a petition seeking rehearing en banc. The Federal Circuit invited the Company to respond to West-Ward’s petition; the Company's responsewas filed in July 2018. In August 2018, the Federal Circuit denied West-Ward's petition for rehearing. In January 2019, West-Ward filed a petition in theUnited States Supreme Court for a writ of certiorari seeking reversal of the Federal Circuit’s decision. The Company submitted a response to that petition onFebruary 12, 2019.In 2015, the Company filed six separate patent infringement lawsuits in the Delaware District Court against Roxane, Inventia Healthcare Pvt. Ltd.(Inventia), Lupin Ltd. and Lupin Pharmaceuticals, Inc. (Lupin), Taro Pharmaceuticals USA, Inc. and Taro Pharmaceutical Industries, Ltd. (Taro), and ApotexInc. and Apotex Corp. (Apotex, and collectively with Roxane, Inventia, Lupin and Taro, the Defendants). The lawsuits each seek an adjudication that therespective Defendants infringed one or more claims of the ‘610 Patent and/or the Company's U.S. Patent No. 9,138,432 (‘432 Patent) by submitting to theFDA an ANDA for a generic version of Fanapt® prior to the expiration of the ‘610 Patent in November 2027 or the ‘432 Patent in September 2025. TheDefendants denied infringement and counterclaimed for declaratory judgment of invalidity and noninfringement of the ‘610 Patent and the ‘432 Patent.Certain Defendants have since entered into agreements resolving these lawsuits, as discussed below. The remaining matters have been stayed until the later ofNovember 30, 2018 or 14 days after98Table of Contentsfinal disposition by the U.S. Supreme Court of any petition for a writ of certiorari filed by West-Ward. The Company entered into a confidential stipulationwith each of Inventia and Lupin regarding any potential launch of Inventia’s and Lupin's generic ANDA products.Lupin filed counter claims for declaratory judgment of invalidity and noninfringement of seven of the Company's method of treatment patents thatare listed in the Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) related to Fanapt® (such seven patents, the Method ofTreatment Patents). The Company has not sued Lupin for infringing the Method of Treatment Patents. In October 2016, the Company, along with Lupin, fileda Stipulation of Dismissal in the Delaware District Court pursuant to which Lupin’s counterclaims relating to the Method of Treatment Patents were dismissedwithout prejudice in recognition of an agreement reached between the parties by which the Company would not assert those patents against Lupin absentcertain changes in Lupin’s proposed prescribing information for its iloperidone tablets.Taro and Apotex each entered into separate License Agreements (together, the License Agreements) resolving these lawsuits in October 2016 andDecember 2016, respectively. The License Agreements grant Taro and Apotex non-exclusive licenses to manufacture and commercialize a version ofFanapt® in the U.S. effective November 2027, unless prior to that date the Company obtains pediatric exclusivity for Fanapt®, in which case, the license willbe effective May 2028. Taro and Apotex each may enter the market earlier under certain limited circumstances. The License Agreements, which are subject toreview by the U.S. Federal Trade Commission (FTC) and the U.S. Department of Justice (DOJ), provide for a full settlement and release of all claims that arethe subject of the respective litigation with Taro and Apotex.In February 2016, Roxane filed suit against the Company in the U.S. District Court for the Southern District of Ohio (Ohio District Court). The suitsought a declaratory judgment of invalidity and noninfringement of the Method of Treatment Patents. In December 2016, the Ohio District Court dismissedRoxane’s suit without prejudice for lack of personal jurisdiction.In February 2016, Roxane filed a Petition for Inter Partes Review (IPR) of the ‘432 Patent with the Patent Trials and Appeals Board (PTAB) of theU.S. Patent and Trademark Office. In August 2016, the PTAB denied the request by Roxane to institute an IPR of the ‘432 Patent. In September 2016, Roxanefiled a Petition for Rehearing with the PTAB. In November 2016, the PTAB denied Roxane’s Petition for Rehearing.HETLIOZ®. In March 2018, the Company received a Paragraph IV certification notice letter from Teva Pharmaceuticals USA, Inc. (Teva) notifyingthe Company that Teva had submitted an ANDA for HETLIOZ® to the FDA requesting approval to market, sell and use a generic version of the 20mgHETLIOZ® capsules for Non-24-Hour-Sleep-Wake Disorder. In its notice letter, Teva alleges that the Company's Orange Book listed U.S. Patent No.RE46,604, U.S. Patent No. 9,060,995, U.S. Patent 9,539,234, U.S. Patent 9,549,913, U.S. Patent 9,730,910 and U.S. Patent 9,885,241 (collectively, the VandaPatents), which cover methods of using HETLIOZ®, are invalid, unenforceable and/or will not be infringed by Teva’s manufacture, use or sale of the productdescribed in its ANDA. The Company received similar notice letters in April 2018 from MSN Pharmaceuticals Inc. and MSN Laboratories Private Limited(together, MSN) and Apotex.In April 2018, the Company filed a patent infringement lawsuit in the Delaware District Court against Teva and in May 2018, the Company filedpatent infringement lawsuits in the Delaware District Court against MSN and Apotex. The lawsuits seek an adjudication that Teva, MSN and Apotex haveinfringed one or more claims of the Vanda Patents by submitting to the FDA an ANDA for a generic version of HETLIOZ® prior to the expiration of the latestto expire of the Vanda Patents in 2034. The relief requested by the Company in the lawsuits includes requests for permanent injunctions preventing Teva,MSN and Apotex from infringing the asserted claims of the Vanda Patents by engaging in the manufacture, use, offer to sell, sale, importation or distributionof generic versions of HETLIOZ® before the last expiration date of the Vanda Patents and for an order that any effective date of FDA approval of Teva, MSN,and Apotex’s generic versions of HETLIOZ® be a date not earlier than the expiration of the Vanda Patents. The lawsuits automatically preclude the FDA fromapproving the submitted ANDAs until the earlier of seven and one-half years after the January 2014 approval of the Company's application for New ChemicalEntity Status or entry of a district court decision finding the Vanda Patents invalid, unenforceable or not infringed. In June 2018, Teva, MSN and Apotexeach answered the Company's complaint, and Teva included counterclaims for declarations that the Vanda Patents are invalid. MSN included additionalcounterclaims for declarations that the Vanda Patents are not infringed. In July 2018, the Company answered Teva and MSN's counterclaims, denying theirallegations.In October 2018, the Company received an additional Paragraph IV certification notice letter from Teva concerning its Orange Book listed U.S.Patent No. 10,071,977, which expires in 2035 (the ‘977 Patent). In November 2018, the Company received a similar additional Paragraph IV certificationnotice letter from Apotex concerning the ’977 Patent. In December 2018, the Company filed amended complaints against Teva, Apotex, and MSN alleginginfringement of one or more claims of the ’977 Patent. The amended complaints seek an adjudication that Teva, Apotex, and MSN have infringed one ormore claims of the ’977 Patent by submitting to FDA an ANDA for a generic version of HETLIOZ® prior to the expiration of the ’97799Table of ContentsPatent. The relief requested by the Company in the amended complaints includes requests for permanent injunctions preventing Teva, Apotex, and MSNfrom infringing the asserted claims of the ’977 Patent by engaging in the manufacture, use, offer to sell, sale, importation or distribution of generic versions ofHETLIOZ® before the expiration date of the ’977 Patent and for an order that any effective date of FDA approval of Teva, MSN, and Apotex’s genericversions of HETLIOZ® be a date not earlier than the expiration of the ’977 Patent. In December 2018, Teva, MSN, and Apotex answered the Company'samended complaints, and Teva and MSN included counterclaims for declarations that the ’977 Patent is invalid, and MSN included an additionalcounterclaim that the ’977 Patent is unenforceable for inequitable conduct. In January 2019, the Company answered Teva and MSN’s counterclaims. A trialdate for these lawsuits has been set for September 2020.In February 2019, the Company received an additional Paragraph IV certification notice letter from Teva concerning its Orange Book listed U.S.Patent No. 10,149,829, which expires in 2033 (the ’829 Patent). In its notice letter, Teva alleges that the ’829 Patent, which covers methods of usingHETLIOZ®, is invalid, unenforceable and will not be infringed by Teva’s manufacture, use or sale of the product described in its ANDA.Other Matters. In April 2018, the Company submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) periodfor patients who had completed the tradipitant Phase II clinical study (2301) in gastroparesis. In May 2018, based on feedback from the FDA, the Companyamended the protocol limiting the duration of treatment in the 2301 study to a total of three months, while continuing to seek further dialogue with the FDAon extending the study duration to 52-weeks. As a part of this negotiation process, in September 2018, the Company submitted a new follow-on 52-weekOLE protocol to the FDA (2302) for patients who had completed the 2301 study. While waiting for further feedback, no patients were ever enrolled in anystudy beyond 12 weeks. On December 19, 2018, the FDA imposed a partial clinical hold (PCH) on the two proposed studies, stating that the Company isrequired first to conduct additional chronic toxicity studies in canines, monkeys or minipigs before allowing patients access in any clinical protocol beyond12 weeks. The PCH was not based on any safety or efficacy data related to tradipitant. Rather, the FDA informed the Company that these additional toxicitystudies are required by a guidance document. The Company believes that the FDA does not have legal authority to issue the PCH on the basis of theguidance at issue. The Company also believes that it has provided the FDA with sufficient information regarding the safety of tradipitant to justify thecontinued study of tradipitant in patients beyond 12 weeks, in accordance with applicable law and FDA regulations. On February 5, 2019, the Company fileda lawsuit against the FDA in the United States District Court for the District of Columbia (DC District Court), challenging the FDA’s legal authority to issuethe PCH, and seeking an order to set it aside. On February 14, 2019, the FDA filed a Motion for Voluntary Remand to the Agency and for a Stay of the Case.The Company intends to continue vigorously pursuing its interests in the matter. The PCH and the Company's plans for tradipitant clinical development arediscussed in greater detail in Part I, Item 1, Business, of this annual report on Form 10-K.On February 4, 2019, a qui tam action filed against the Company was unsealed by order of the DC District Court entered on January 31, 2019. Thequi tam action, United States ex rel. Richard Gardner v. Vanda Pharmaceuticals Inc., which was filed under seal on March 10, 2017, was brought by a formerCompany employee on behalf of the U.S., 28 states and the District of Columbia (collectively, the Plaintiff States) and the policyholders of certain insurancecompanies under the Federal False Claims Act and state law equivalents to the Federal False Claims Act and related state laws. The complaint alleges that theCompany violated these laws through the promotion and marketing of its products Fanapt® and HETLIOZ®. The complaint seeks, among other things, trebledamages, civil penalties for each alleged false claim, and attorneys’ fees and costs.The Company has not been served with the qui tam complaint. By virtue of the court having unsealed the case, it learned that on January 29, 2019,the U.S., as well as the Plaintiff States, filed notice of their election not to intervene in the qui tam action at this time. The U.S.’ and the Plaintiff States’election not to intervene does not prevent the plaintiff/relator from litigating this action and the U.S. and the Plaintiff States may later seek to intervene in theaction. The Company intends to vigorously defend itself in the litigation if served.100Table of Contents17. Quarterly Financial Data (Unaudited)The following is a summary of quarterly financial data for the years ended December 31, 2018 and 2017:(in thousands, except for per share amounts)FirstQuarter SecondQuarter ThirdQuarter FourthQuarterYear Ended December 31, 2018 Revenues$43,592 $47,350 $49,135 $53,041Gross profit (1)38,680 41,739 43,670 46,994Income from operations2,442 3,913 6,233 9,150Net income3,066 4,611 7,171 10,360Net income per share, basic$0.07 $0.09 $0.14 $0.20Net income per share, diluted$0.06 $0.09 $0.13 $0.19Year Ended December 31, 2017 Revenues$37,415 $42,056 $41,336 $44,276Gross profit (1)32,958 37,095 36,379 39,053Loss from operations(7,906) (1,924) (4,923) (2,150)Net loss(7,645) (1,534) (4,550) (1,838)Net loss per share, basic and diluted$(0.17) $(0.03) $(0.10) $(0.04) (1)Gross profit includes revenues less cost of goods sold, excluding amortization, and less intangible asset amortization.101Table of ContentsVANDA PHARMACEUTICALS INC.EXHIBIT INDEX ExhibitNumber Description 3.1 Form of Amended and Restated Certificate of Incorporation of the registrant (filed as Exhibit 3.8 to Amendment No. 2 to the registrant’sregistration statement on Form S-1 (File No. 333-130759) on March 17, 2006 and incorporated herein by reference). 3.2 Fourth Amended and Restated Bylaws of the registrant, as amended and restated on December 17, 2015 (filed as Exhibit 3.1 to the registrant’scurrent report on Form 8-K (File No. 001-34186) on December 21, 2015 and incorporated herein by reference). 4.1 Specimen certificate representing the common stock of the registrant (filed as Exhibit 4.4 to Amendment No. 2 to the registrant’s registrationstatement on Form S-1 (File No. 333-130759) on March 17, 2006, and incorporated herein by reference). 10.1# Amended and Restated License, Development and Commercialization Agreement, dated July 24, 2005, by and between Bristol-Myers SquibbCompany and the registrant (relating to HETLIOZ®) (filed as Exhibit 10.3 to Amendment No. 1 to the registrant’s registration Statement onForm S-1 (File No. 333-130759) on February 16, 2006 and incorporated herein by reference). 10.2 Form of Indemnification Agreement entered into by directors and executive officers (filed as Exhibit 10.11 to the registrant’s registrationstatement on Form S-1 (File No. 333-130759) on December 29, 2005 and incorporated herein by reference). 10.3† 2006 Equity Incentive Plan, as amended (filed as Exhibit 10.17 to Amendment No. 2 to the registrant’s Registration Statement on Form S-1(File No. 333-130759), as filed on March 17, 2006, and incorporated herein by reference). 10.4† Amended and Restated Employment Agreement, dated December 16, 2008, by and between Mihael H. Polymeropoulos and the registrant(filed as Exhibit 10.34 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on August 10, 2009 and incorporated herein byreference). 10.5† Employment Agreement, dated December 13, 2010, by and between James Kelly and the registrant (filed as Exhibit 10.38 to the registrant’sannual report on Form 10-K (File No. 001-34186) on March 10, 2011 and incorporated herein by reference). 10.6† Amendment to Amended and Restated Employment Agreement, dated December 16, 2010, by and between Mihael H. Polymeropoulos andthe registrant (filed as Exhibit 10.39 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 10, 2011 and incorporatedherein by reference). 10.7 Amended and Restated Tax Indemnity Agreement, dated December 16, 2010, by and between Mihael H. Polymeropoulos and the registrant(filed as Exhibit 10.41 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 10, 2011 and incorporated herein byreference). 10.8 Lease, effective as of July 25, 2011, by and between Square 54 Office Owner LLC and the registrant (filed as Exhibit 10.42 to the registrant’squarterly report on Form 10-Q (File No. 001-34186) on November 7, 2011 and incorporated herein by reference). 10.9 Amendment to Amended and Restated License, Development and Commercialization Agreement, dated as of April 15, 2010, by and betweenBristol-Myers Squibb Company and the registrant (filed as Exhibit 10.38 to the registrant’s current report on Form 8-K (File No. 001-34186)on April 19, 2010 and incorporated herein by reference). 10.10 Amendment to Amended and Restated License, Development and Commercialization Agreement, dated as of May 24, 2012, by and betweenBristol-Myers Squibb Company and the registrant (filed as Exhibit 10.46 to the registrant’s current report on Form 8-K (File No. 001-34186)on May 30, 2012 and incorporated herein by reference). 10.11# License, Development and Commercialization Agreement, dated as of April 12, 2012, by and between Eli Lilly and Company and theregistrant (filed as Exhibit 10.48 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on August 3, 2012 and incorporatedherein by reference). 10.12 Amendment to Amended and Restated License, Development and Commercialization Agreement, dated as of April 25, 2013, by and betweenBristol-Myers Squibb Company and the registrant (filed as Exhibit 10.50 to the registrant’s current report on Form 8-K (File No. 001-34186)on April 29, 2013 and incorporated herein by reference).102Table of ContentsExhibitNumber Description 10.13# Manufacturing Agreement, dated January 24, 2014, by and between Patheon Pharmaceuticals Inc. and the registrant (relating to HETLIOZ®)(filed as Exhibit 10.53 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 8, 2014 and incorporated herein byreference). 10.14 Amendment to Lease Agreement, dated March 18, 2014, by and between Square 54 Office Owner LLC and the registrant (filed as Exhibit10.54 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 8, 2014 and incorporated herein by reference). 10.15 Settlement Agreement and Mutual General Release, dated December 22, 2014, by and among Novartis Pharma AG and the registrant (filed asExhibit 10.55 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by reference). 10.16# Asset Transfer Agreement, dated December 22, 2014, by and among Novartis Pharma AG, Novartis AG and the registrant (relating to Fanapt®)(filed as Exhibit 10.56 to the registrant’s annual report on Form 10-K/A (File No. 001-34186) on June 10, 2015 and incorporated herein byreference). 10.17# Sublicense Agreement, dated November 20, 1997, by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG (filed as Exhibit10.30 to Titan Pharmaceutical Inc.’s registration statement on Form S-3 (File No. 333-42367) on December 16, 1997 and incorporated hereinby reference). 10.18# Amendment No. 1 to Sublicense Agreement by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG, dated November 30, 1998(filed as Exhibit 10.58 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein byreference). 10.19# Amendment No. 2 to Sublicense Agreement, dated April 10, 2001, by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG (filedas Exhibit 10.59 to the registrant’s annual report on Form 10-K/A (File No. 001-34186) on June 10, 2015 and incorporated herein byreference). 10.20# Amendment No. 3 to Sublicense Agreement, dated June 4, 2004, by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG (filed asExhibit 10.60 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by reference). 10.21 Stock Purchase Agreement, dated December 22, 2014, by and between Novartis AG and the registrant (filed as Exhibit 10.61 to theregistrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by reference). 10.22# License Agreement, dated December 22, 2014, by and between Novartis Pharma AG and the registrant (relating to AQW051) (filed as Exhibit10.62 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by reference). 10.23† Employment Agreement, dated September 3, 2015, by and between Gian Piero Reverberi, Senior Vice President and General Manager Europe,and the registrant (filed as Exhibit 10.64 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on November 4, 2015 andincorporated herein by reference). 10.24 Agreement, dated February 2, 2016, by and among Titan Pharmaceuticals, Inc., Aventisub LLC, the successor-in-interest to Aventisub II Inc.Sanofi-Aventis and the registrant (filed as Exhibit 10.1 to the registrant’s current report on Form 8-K (File No. 001-34186) on February 4, 2016and incorporated herein by reference). 10.25† Vanda Pharmaceuticals Inc. Amended and Restated 2016 Equity Incentive Plan, effective as of June 13, 2018 (filed as Exhibit 10.1 to theregistrant’s registration statement on Form S-8 (File No. 333-225599) on June 13, 2018 and incorporated herein by reference). 10.26† Form of Notice of Stock Option Grant and Stock Option Agreement under Amended and Restated 2016 Equity Incentive Plan (filed as Exhibit10.2 to the registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by reference). 10.27† Form of Restricted Stock Unit Award Agreement under Amended and Restated 2016 Equity Incentive Plan (filed as Exhibit 10.3 to theregistrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by reference). 10.28† UK Sub Plan under the Amended and Restated 2016 Equity Incentive Plan (filed as Exhibit 10.4 to the registrant’s registration statement onForm S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by reference). 10.29† Form of Stock Option Grant and Stock Option Agreement under the UK Sub Plan under the Amended and Restated 2016 Equity IncentivePlan (filed as Exhibit 10.5 to the registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporatedherein by reference). 103Table of ContentsExhibitNumber Description10.30† Form of Restricted Stock Unit Award Agreement under the UK Sub Plan under the Amended and Restated 2016 Equity Incentive Plan (filed asExhibit 10.6 to the registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein byreference). 10.31# Manufacturing Agreement, dated May 6, 2016, by and between Patheon Pharmaceuticals Inc. and the registrant (relating to Fanapt®) (filed asExhibit 10.42 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on July 28, 2016 and incorporated herein by reference). 10.32 Second Amendment to Lease Agreement, dated June 20, 2016, by and between Square 54 Office Owner LLC and the registrant (filed asExhibit 10.43 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on July 28, 2016 and incorporated herein by reference). 10.33 Sublease Agreement, dated June 22, 2016, by and between Hunton & Williams LLP and the registrant (filed as Exhibit 10.44 to theregistrant’s quarterly report on Form 10-Q (File No. 001-34186) on July 28, 2016 and incorporated herein by reference). 10.34# License Agreement, dated October 24, 2016, by and among Taro Pharmaceuticals USA, Inc., Taro Pharmaceuticals Industries Ltd. and theregistrant (filed as Exhibit 10.45 to the registrant’s annual report on Form 10-K (File No. 001-34186) on February 17, 2017 and incorporatedherein by reference). 10.35# License Agreement, dated December 7, 2016, by and between Apotex, Inc. and the registrant (filed as Exhibit 10.46 to the registrant’s annualreport on Form 10-K (File No. 001-34186) on February 17, 2017 and incorporated herein by reference). 10.36 Third Amendment to Lease Agreement, dated March 28, 2018, by and between Square 54 Office Owner LLC and the registrant (filed asExhibit 10.38 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 2, 2018 and incorporated herein by reference). 10.37 Fourth Amendment to Lease Agreement, dated March 29, 2018, by and between Square 54 Office Owner LLC and the registrant (filed asExhibit 10.39 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 2, 2018 and incorporated herein by reference). 10.38† Amended and Restated Employment Agreement, dated April 30, 2018, by and between Gunther Birznieks and the registrant (filed as Exhibit10.40 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 2, 2018 and incorporated herein by reference). 10.39† Employment Agreement, dated August 13, 2018, by and between Timothy Williams and the registrant (filed as Exhibit 10.41 to theregistrant’s quarterly report on Form 10-Q (File No. 001-34186) on November 7, 2018 and incorporated herein by reference). 21.1 List of Subsidiaries (filed as Exhibit 21.1 to the registrant’s annual report on Form 10-K (File No. 001-34186) on February 17, 2017 andincorporated herein by reference). 23.1* Consent of PricewaterhouseCoopers LLP, Independent Registered Public Accounting Firm. 31.1* Certification of the Chief Executive Officer, as required by Section 302 of the Sarbanes-Oxley Act of 2002. 31.2* Certification of the Chief Financial Officer as required by Section 302 of the Sarbanes-Oxley Act of 2002. 32.1* Certification of the Chief Executive Officer and Chief Financial Officer as required by Section 906 of the Sarbanes-Oxley Act of 2002. 101* The following financial information from this annual report on Form 10-K for the fiscal year ended December 31, 2018, formatted in XBRL(eXtensible Business Reporting Language) and furnished electronically herewith: (i) Consolidated Balance Sheets as of December 31, 2018and 2017; (ii) Consolidated Statements of Operations for the years ended December 31, 2018, 2017 and 2016; (iii) Consolidated Statements ofComprehensive Income (Loss) for the years ended December 31, 2018, 2017 and 2016; (iv) Consolidated Statements of Changes inStockholders’ Equity for the years ended December 31, 2018, 2017 and 2016; (v) Consolidated Statements of Cash Flows for the years endedDecember 31, 2018, 2017 and 2016; and (vi) Notes to the Consolidated Financial Statements. † Indicates management contract or compensatory plan. # Confidential treatment has been granted with respect to certain provisions of this exhibit. * Filed herewith.104Exhibit 23.1CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRMWe hereby consent to the incorporation by reference in the Registration Statements on Form S-8 (No. 333-133368, No. 333-138070, No. 333-141571,No. 333-148924, No. 333-156995, No. 333-164567, No. 333-171962, No. 333-179265, No. 333-186509, No. 333-193614, No. 333-201754, No. 333-209144, No. 333-212255, No. 333-218774 and No. 333-225599) of Vanda Pharmaceuticals Inc. of our report dated February 19, 2019 relating to thefinancial statements and the effectiveness of internal control over financial reporting, which appears in this Form 10-K./s/ PricewaterhouseCoopers LLPBaltimore, MarylandFebruary 19, 2019EXHIBIT 31.1CERTIFICATION OF CHIEF EXECUTIVE OFFICERPURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002I, Mihael H. Polymeropoulos, certify that:1.I have reviewed this annual report on Form 10-K of Vanda Pharmaceuticals Inc.;2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by thisreport;3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;4.The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined inExchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision,to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others withinthose entities, particularly during the period in which this report is being prepared;b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements forexternal purposes in accordance with generally accepted accounting principles;c.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about theeffectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; andd.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s mostrecent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likelyto materially affect, the registrant’s internal control over financial reporting; and5.The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, tothe registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which arereasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; andb.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internalcontrol over financial reporting.February 19, 2019 /s/ Mihael H. Polymeropoulos, M.D. Mihael H. Polymeropoulos, M.D. President and Chief Executive Officer(Principal Executive Officer)EXHIBIT 31.2CERTIFICATION OF CHIEF FINANCIAL OFFICERPURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002I, James P. Kelly, certify that:1.I have reviewed this annual report on Form 10-K of Vanda Pharmaceuticals Inc.;2.Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by thisreport;3.Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;4.The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined inExchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:a.Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision,to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others withinthose entities, particularly during the period in which this report is being prepared;b.Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements forexternal purposes in accordance with generally accepted accounting principles;c.Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about theeffectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; andd.Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s mostrecent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likelyto materially affect, the registrant’s internal control over financial reporting; and5.The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, tothe registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):a.All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which arereasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; andb.Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internalcontrol over financial reporting.February 19, 2019 /s/ James P. Kelly James P. KellyExecutive Vice President, Chief Financial Officer and Treasurer(Principal Financial Officer and Principal Accounting Officer)EXHIBIT 32.1CERTIFICATION OF CHIEF EXECUTIVE OFFICER AND CHIEF FINANCIAL OFFICERPursuant to Section 906 of the Sarbanes-Oxley Act of 2002(Subsections (a) and (b) of Section 1350, Chapter 63 of Title 18, United States Code)Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 (subsections (a) and (b) of section 1350, chapter 63 of title 18, United States Code), each of theundersigned officers of Vanda Pharmaceuticals Inc., (the “Company”), does hereby certify, to the best of such officer’s knowledge, that:The Annual Report on Form 10-K for the year ended December 31, 2018 (the Form 10-K) of the Company fully complies with the requirements ofSection 13(a) or 15(d) of the Securities Exchange Act of 1934, and the information contained in the Form 10-K fairly presents, in all material respects, theconsolidated financial condition and results of operations of the Company.February 19, 2019 /s/ Mihael H. Polymeropoulos, M.D. Mihael H. Polymeropoulos, M.D.President and Chief Executive Officer(Principal Executive Officer) February 19, 2019 /s/ James P. Kelly James P. KellyExecutive Vice President, Chief Financial Officer and Treasurer(Principal Financial Officer and Principal Accounting Officer)A signed original of this written statement required by Section 906 has been provided to the Company and will be retained by the Company and furnishedto the Securities and Exchange Commission (SEC) or its staff upon request. This certification “accompanies” the Form 10-K to which it relates, is notdeemed filed with the SEC and is not to be incorporated by reference into any filing of the Company under the Securities Act of 1933, as amended, or theSecurities Exchange Act of 1934, as amended (whether made before or after the date of the Form 10-K), irrespective of any general incorporation languagecontained in such filing.

Continue reading text version or see original annual report in PDF format above